Abstract：Objective：To observe the clinical effect of Shugan Jieyu capsules combined with venlafaxine for depression. Methods：A total of 300 cases of patients with depression were selected and randomly divided into the control group and the treatment group， 150 cases in each group. The control group was given venlafaxine， and the treatment group was additionally treated with Shugan Jieyu capsules based on the treatment of the control group. Both groups were treated for eight weeks. The clinical effect and adverse reactions were compared between the two groups. Before and after treatment， levels of inflammatory factors and neurotransmitters in serum were compared between the two groups. Results：The total effective rate was 94.00% in the treatment group，higher than that of 87.33% in the control group(P＜0.05). After treatment， levels of high-sensitivity C-reactive protein(hs-CRP)，interleukin-2(IL-2) and tumor necrosis factor- α(TNF- α) in serum in the two groups were decreased when compared with those before treatment(P＜0.05)， and the three levels above in the treatment group were lower than those in the control group(P＜0.05). After treatment， levels of dopamine(DA)， norepinephrine(NE)，and 5-hydroxytryptamine(5-HT) in serum in the two groups were increased when compared with those before treatment(P＜0.05)，and the three levels above in the treatment group were higher than those in the control group(P＜ 0.05). The incidence of adverse reactions was 8.67% in the treatment group，and 6.67% in the control group，no significance being found in the difference(P＞0.05). Conclusion： The therapy of Shugan Jieyu capsules combined with venlafaxine for depression can effectively improve clinical effect， whose mechanism maybe related to the regulation on levels of inflammatory factors and neurotransmitters.