Objective To explore the effect on efficacy and safety of Wuling capsule on patients with post-stroke depression.Methods From July 2012 to September 2014, 90 post-stroke depression patients were selected in our hospital.The patients were divided into treatment group (n=45) and control group (n=45) by random number table method.The post-stroke depression patients in control group were treated with fluoxetine as clinical drug program.The post-stroke depression patients in treatment group were treated with Wuling capsule as clinical drug program, six weeks for a course of treatment, both group were treated after two courses,the clinical indicators improve effect, clinical treatment, changes of cytokines, incidence of adverse reactions of the patients between two groups were compared and analyzed.Results Hamilton depression scale (HAMD) scores and Barther index (BI) scores of patients in treatment group post-treatment were better than control group (P<0.05) .Compared with control group, the ratio of clinical efficiency and total efficiency significant in treatment group were increased significantly (P<0.05).The patients in treatment group post-treatment, the levels of cytokine of interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) decreased significantly (P<0.05) .Compared with control group, the incidences of adverse effect of patients in treatment group were decreased (P<0.05).Conclusions Wuling capsule has certain therapeutic advantages for improving clinical efficacy and reducing adverse reactions for patients with post-stroke depression.It could as the therapy of choice for post-stroke depression patients.