Abstract： Objective： To observe the clinical effect of Jieyu Huatang tang in the treatment of depression after cerebral infarction and its effect on the changes of brain-derived neurotrophic factor(BDNF) ， Substance P(SP) and 5-hydroxytryptamine(5-HT) in serum. Methods：A total of 86 patients with depression after cerebral infarction were selected and divided into the control group and the observation group according to random number table，43 cases in each group. The control group was treated with quetiapine fumarate tablets and the observation group was additionally treated with Jieyu Huatang tang based on the treatment of the control group. The clinical effect in the two groups was compared， and the changes in the scores of Hamilton Depression Scale(HAMD)， Pittsburgh Sleep Quality Index(PSQI)， Stroke Rehabilitation Assessment of Movement(STREAM) and National Institutes of Health Stroke Scale(NIHSS) before and after treatment were observed；the levels of BDNF，SP and 5-HY in serum were detected. Results：The total effective rate was 93.02% in the observation group， higher than that of 72.09% in the control group， the difference being significant(P＜0.05). Before treatment， there was no significant difference in the comparison of the scores of HAMD， PSQI， STREAM and NIHSS between the two groups(P＞0.05). After treatment， the scores of HAMD， PSQI and NIHSS in the two groups were decreased when compared with those before treatment，and the STREAM score was increased when compared with that before treatment(P＜0.05)；the scores of HAMD，PSQI and NIHSS in the observation group were lower than those in the control group and the STREAM score was higher(P＜0.05). Before treatment， there was no significant difference in the comparison of the levels of BDNF，SP and 5-HY in serum between the two groups(P＞0.05). After treatment，the levels of BDNF and 5-HY in serum were increased when compared with those before treatment，and SP level was decreased when compared with that before treatment(P＜0.05)；the levels of BDNF and 5-HY in the observation group were higher than those in the control group and the SP level was lower(P＜0.05). Conclusion： Jieyu Huatang tang has significant clinical effect in treating patients with depression after cerebral infarction， which can relive their depressive mood， improve the quality of sleep，motor function and nerve function，increase the levels of BDNF and 5-HY in serum，and reduce the SP level.