Abstract: OBJECTIVE To explore the effects of Chaihu Shugan powder combined with venlafaxine on T-lymphocytes subgroup and natural killer cell (NK cell) in patients with depression. METHODS Twenty patients treated by chaihu Shugan powder combined with venlafaxine were assigned to trial group, and the other twenty-one patients treated by venlafaxine alone were assigned to control group. Serum levels of T-lymphocytes subgroups and express percent of NK cell between the two groups were compared before treatment and four weeks after treatment respectively in both treatment and control groups. RESULTS Significant difference was found in the serum levels of T cell (maker: CD3⁺), helper T cell(phenotypic marker: CD4⁺) and NK cell in the trial group after treatment(P<0.05), CD3⁺, CD4⁺ and CD8⁺ T cell declined significantly after treatment in both trial and control group(P<0.05). In addition, serum level of CD8⁺ was negatively associated with HAMD score of patients with depression(P<0.05). Furthermore, incidence of adverse reaction was lower in the trial group than that in the control group. CONCLUSION Chaihu Shugan powder can improve immune function of patients with depression and decrease the adverse reaction of antidepressants.