Abstract: OBJECTIVE To study effect of Xingnao Jieyu prescription combined with massage therapy for post stroke depression(PSD).METHODS A total of 100 consecutive PSD inpatients from October 2016 to October 2017 were enrolled and divided randomly into the control group and the observation group, with 50 cases in each group. The patients in the control group received fluoxetine hydrochloride capsules combined with massage therapy and the observation group adopted Xingnao Jieyu prescription combined with massage therapy for 21 d as 1 period. Compare national institutes of health stroke scale(NIHSS), Hamilton depression scale(HAMD), modify Barthel Index(MBI), effect, side effect, serum 5-Hydroxytryptamine(5-HT), interleukin-6(IL-6) and tumor necrosis factor alpha(TNF-α).RESULTS Before treatment, the NIHSS, HAMD, MBI, 5-HT, IL-6 and TNF-α in 2 groups were comparable(P>0.05). Compared with the before treatment, the NIHSS, HAMD, 5-HT, IL-6 and TNF-α were decreased(P<0.05), MBI was increased in 2 groups (P<0.05). Compared with the control group, the NIHSS, HAMD, 5-HT, IL-6 and TNF-α were decreased (P<0.05), MBI had increased in the observation group (P<0.05). The effective cases and the total efficacy rate in the observation group were more (P<0.05). There were no severe adverse drug reactions in 2 groups.CONCLUSION It is better short-term safety and effectiveness of Xingnao Jieyu prescription combined with massage therapy for PSD patients.