Abstract： Objective： To observe the clinical effect of Chaigui Wendan Dingzhi Decoction combined with Agomelatine Tablets for depression and its effect on the levels of 5- hydroxytryptamine (5- HT) and tryptophan hydroxylase (TPH) in serum. Methods： A total of 96 cases of patients with depression were selected and divided into the observation group and the control group according to the random number table method，with 48 cases in each group. The control group was treated with Agomelatine Tablets，and the observation group was additionally treated with Chaigui Wendan Dingzhi Decoction based on the treatment of the control group. The curative effect，the scores of Hamilton Depression Scale (HAMD) and Self-rating Depression Scale (SDS)， and the levels of 5- HT and TPH in serum were compared between the two groups. Results：The total effective rate was 93.75% in the observation group and 81.25% in the control group， the difference being significant (P＜0.05). Before treatment， there was no significant difference being found in the comparison of the scores of HAMD and SDS between the two groups (P＞0.05). After treatment，the scores of HAMD and SDS in the two groups were decreased when compared with those before treatment (P＜0.05)，and the scores of HAMD and SDS in the observation group were lower than those in the control group (P＜0.05). Before treatment，there was no significant difference being found in the comparison of the levels of 5- HT and TPH between the two groups (P＞0.05). After treatment， the levels of 5-HT and TPH in the two groups were increased when compared with those before treatment (P＜ 0.05)，and the levels of 5-HT and TPH in the observation group were higher than those in the control group (P＜0.05). Conclusion：Chaigui Wendan Dingzhi Decoction combined with Agomelatine Tablets for depression can improve the clinical effect and neurotransmitter levels， and effectively improve the symptoms of depression.