Abstract: Objective To observe effect of Chaihu Longgu Muli Decoction combined with anti-depressant for post-stroke depression patients. Methods A total of 70 patients with post-stroke depression were selected as the study objects, and were randomly divided into control group and study group by random number table method. Both groups were given routine treatment, the control group(n=35)was treated with fluoxetine hydrochloride capsule, and the study group(n=35)was treated with Chaihu Longgu Muli Decoction based on the control group. Clinical curative effect, adverse reactions, Hamilton Depression Scale(HAMD)score before and after treatment, National Institutes of Health Stroke Scale(NIHSS)score, Ability of Daily Life(ADL)score, inflammatory factors ［tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), interleukin-6(IL-6)］ levels were compared in two groups. Results The total effective rate of the study group was 94.3%, which was higher than 74.3% of the control group(P<0.05). After treatment, the scores of HAMD and NIHSS in the study group were lower than those in the control group, ADL score was higher than that of the control group(P<0.01). After treatment, levels of TNF-α, IL-1 and IL-6 in the study group were significantly lower than those in the control group(P<0.01). The incidence of adverse drug reactions was 8.6% in the study group and 5.7% in the control group, but no significant difference was found(P>0.05). Conclusion The combination of Chaihu Longgu Muli Decoction and anti-depressant has a significant effect for the patients with post-stroke depression, which can improve status of depression, - enhance daily life, and reduce inflammatory factors.