Abstract：Objective：To observe the clinical effect of acupuncture combined with occupational therapy (OT) for post-stroke depression(PSD)，and its effects on the level of 5-hydroxytryptamine(5-HT). Methods： A total of 120 cases of PSD patients were selected and divided into the control group and the combination group according to the random number table method， with 60 cases in each group. Both groups were treated with symptomatic treatment of western medicine；the control group was additionally treated with OT， and the combination group was additionally treated with acupuncture based on the treatment of the control group. Both groups were treated for one month. Scores of 24- Item Hamilton Depression Scale (HAMD- 24)，National Institutes of Health Stroke Scale(NIHSS) and 36- Item Short Form Survey(SF- 36)， and levels of 5- HT before and after treatment in the two groups were compared. Results： After treatment，the scores of HAMD- 24 and NIHSS in the two groups were decreased when compared with those before treatment(P＜0.05)，and the scores of HAMD-24 and NIHSS in the combination group were lower than those in the control group(P＜0.05)； SF- 36 scores in the two groups were increased when compared with those before treatment(P＜0.05)， and SF- 36 score in the combination group was higher than that in the control group(P＜0.05). After treatment， 5- HT levels in the two groups were increased when compared with those before treatment(P＜0.05)，and the level in the combination group was higher than that in the control group(P＜0.05). Conclusion： Acupuncture combined with OT can effectively alleviate the depression status of PSD patients，and improve their neurological function，quality of life and 5-HT levels.