To observe the clinical curative effect of Xiaoyao powder in combination with sertraline on post-stroke depression, and analyze the related mechanism. Methods:Forty patients with post-stroke depression in Weinan Central Hospital during January 2014 to January 2015 were randomly divided into the control group and the observation group. Patients of both groups accepted related neurology treatment and nursing intervention. The control group was added sertraline, and the observation group was added Xiaoyao powder on the basis of treatment of the control group. Both groups had a treatment course of 8 weeks. Patients were observed changes in Hamilton depression scale (HAMD), Pittsburgh sleep quality index scale (PSQI), Fugl-Mayer assessment scale (FMA) and the concentration of monoamine neurotransmitter metabolic before treatment, 4 weeks and 8 weeks after treatment. Results:1) HAMD scores, SQI scores and FMA scores in the two groups of patients before treatment were with no statistical differences (P>0.05), however, with clinical interventions, HAMD scores, SQI score and FMA score of the two groups of patients improved after 4 weeks treatment (P<0.05), but differences between the two groups were still not statistically significant (P>0.05). With further treatment, the patients of the two groups were further improved in HAMD scores, SQI score and FMA score. In Addition, compared with the control group, the improvement of the observation group was more significant with statistical difference (P<0.05); 2) After treatment, the concentration of 5-HT and NE increased, as the concentration 5-HIAA declined. The tendency of changes in the observation group was more significant (P<0.05). As the treatment duration processed, limb function improvement of the patients was more significant, and neurotransmitter concentrations changes were more significant. Conclusion:Xiaoyao powder can improve the symptom of depression and somnipathy in patients with post stroke depression, and its mechanism may be related to the mediation of monoamine neurotransmitter metabolism.