Mark first appears in season two. Mark supports Derek when Meredith comes close to dying lexie grey drowning, and the two are able to rekindle their friendship.
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It is eventually revealed that he and Derek grew up together and that he, having lost his mother as a child and his father emotionally neglecting him, considered Derek’s mother as his maternal figure. As he was an only child and Derek was the only son, they became close friends and he was Derek’s best man at the latter’s wedding to Addison. Mark allows her to move in with him, which upsets Lexie. When Lexie makes it clear that she knew that Mark would choose his own daughter over her, she puts an end to their relationship. Sloan experiences difficulties in her pregnancy, so Mark takes her to LA to be treated.
In the sixth-season finale, a gunman commits mass murder at the hospital. Mark helps Lexie save Alex, her new boyfriend. In the aftermath of the shooting, Lexie has a nervous breakdown and Mark has her committed to the psychiatric unit. Their friendship is strained, however Lexie softens towards him when she learns that he is still in love with her. In the meanwhile, Callie and Mark’s daughter is born. Lexie replies that she is still in love with him, but right now she needs Jackson to be happy.