L ana eventually decided to join Metropolis University and in order to remain close with Chloe, moved into her dorm. However, with Chloe remaining a close confidant of Clark's and knowing his secret, Lana confided less in Chloe about problems in her relationship with Clark. Nevertheless, both Lana and Chloe continued to look out for each other and provide help when needed. When Chloe was possessed by Gretchen Winters and began to act strangely, Lana was concerned for her friend and requested Lex's help to get her transferred to Belle Reeve for professional help. In turn, Chloe expressed concern when Lana started to act strangely after spending a lot of time with some medical students. She discovered that Lana was addicted to a drug that gave her near-death experiences. Despite offering help, Lana didn't trust her friend and continued with her dangerous actions until Clark stopped her.

Chloe also expressed concern over Lana's growing relationship with Lex, as she didn't trust him.

This angered Lana and told her to mind her own business. Chloe decided to give her some space to preserve their relationship, but as Lana's relationship with Lex grew, she became more distanced from Lana.

Becoming ever more distanced from Chloe, Lana moved in with Lex. Clearly getting over her past lack of trust of Chloe, Lana eventually confided in her, before taking a step to consummate her relationship with Lex. Chloe patiently listened, as Lana admitted that she was having trust issues, but she really didn't trust herself. Sympathizing with her friend and finally understanding her relationship with Lex, Chloe encouraged Lana to take a step to get what she wanted.
As Lana became concerned about Lex's secretive business, she realized how valuable her relationship with Chloe was and began to confide in her again. When Lana fainted in the middle of their conversation, Chloe became concerned for her health but Lana convinced her to keep it secret. She later revealed her secret to Chloe.

And Lana confessed that she regretted all her decisions over the past few months. Chloe was surprised but sympathetic and hugged her tightly.
Bringing their friendship closer again, Lana called Chloe, extremely upset, and asked her to help her find Lex, after he disappeared in front of her eyes. Lana and Chloe arrived at the mansion but they didn't find anything. However, Lex was there on another reality frequency. Chloe and Lana, with the help of Jimmy Olsen, were eventually able to free Lex.
Lana soon confessed to Chloe that she had reservations for marrying Lex due to her lingering feelings for Clark. When their conversation was published by Linda Lake, Lana accused Chloe of gossiping about her. Chloe denied this, claiming she would never betray Lana like that and she should give her the benefit of the doubt.

Lana did, but still believed that Chloe was helping Clark hide something from her. Lana realized she left things in a weird place with Chloe and visited her to say that she would quit asking Chloe about Clark's secret if Chloe admitted that he had one. She then asked Chloe to be her Maid-of-Honor.

Lana and Chloe lived with each other again briefly when Lana received death threats whilst Lex was out of town. Whilst there, Lana started snooping on Chloe's computer again, attempting to access a file titled, "CK", without any luck. Lana only invited Chloe to her bachelorette party, indicating how important Chloe was to her.

Despite this, she used Chloe as bait to expose Clark's secret by locking her in a wine cellar, knowing that Chloe would rely on Clark to save her.
Chloe eventually suspected that Lana had discovered Clark's secret when Lana confessed to Chloe that she had married Lex to protect Clark. Lana, once again, put her trust in Chloe to keep this a secret, but Lana's dangerous scheme stuck in the middle of Lex, Clark and Lionel's secrets led to her car blowing up, seemingly killing her.

After Chloe's healing power manifested itself, she woke up in the Smallville Medical Center morgue. To remove all evidence of her power, she took her death certificate and found Lana's death certificate underneath it. Chloe was shocked and saddened by this discovery.

However, it was eventually revealed that Lana had faked her death. Nevertheless, when she returned to Smallville, Lana didn't see Chloe for a while.
Chloe made several attempts to overcome her new meteor freak status, which led her to the Isis Foundation. She was shocked to discover that Lana was running it. Whilst Lana trusted Chloe to keep her involvement with the Foundation a secret, Chloe did not return this trust and kept her meteor ability a secret, claiming that she was there as a journalist.

When Lana accidentally obtained Clark's powers via electricity, she acted very irresponsibly and violently attacked Grant Gabriel, Lois Lane and Lex Luthor, giving Chloe cause for concern. Once her powers were revoked, Chloe confronted Lana about her behavior. Chloe admitted that she didn't believe Lana was malevolent but gave her a friendly warning that she would not let her hurt Clark. Their friendship was strained after this and they didn't see much of each other, as they both remained busy with work.
Chloe was devastated when Lana was attacked by Brainiac and left in a coma. She visited her in hospital and shed a tear at the loss of her friend.

After Lana's recovery, she left Smallville but visited the Isis Foundation, where Chloe found her crouched by a radiator.

Chloe was excited to see her again and Lana congratulated Chloe on her hard work at transforming the Isis Foundation into a fully functioning organization. They briefly discussed Clark, but Lana insisted that her reappearance be kept secret from him. Chloe reluctantly agreed.
Chloe didn't see Lana again until she arrived as a surprise guest at her wedding to Jimmy. Chloe again was thrilled to see Lana, but their reunion was brief as Doomsday then crashed the wedding and kidnapped Chloe.
Concerned for her friend, Lana helped Clark track down Chloe, who was eventually exorcised of Brainiac and returned home. Chloe's jealousy of Clark's love for Lana had clearly gone by this point in her life as she actively encouraged Clark to re-address his feelings for Lana.

When Lana went missing, Chloe was concerned for Lana's safety and wondered what it was that she was doing by the radiator that day in the Isis Foundation. Behind it, Clark and Chloe discovered a vital clue to Lana's whereabouts, which led them to Dr Groll's lab, where Lana was found with the Prometheus suit.
Chloe and Lana last saw each other after Lana had absorbed all of the kryptonite from Lex's bomb with the Prometheus suit. Chloe consoled her, as this had made Lana permanently separated from Clark. They hugged each other goodbye for a final time