Abstract： Objective： To observe the clinical effect of Zishen Kaiyu Anshen tang combined with Fluoxetine Hydrochloride Capsules for depression. Methods： A total of 102 cases of patients with depression with syndrome of non-interaction between the heart and kidney were retrospectively analyzed and divided into the control group and the observation group according to different treatment methods， with 50 and 52 cases in each group respectively. The control group was given Fluoxetine Hydrochloride Capsules，and the observation group was treated with Zishen Kaiyu Anshen tang. The course of treatment in the two groups was six weeks. The levels of norepinephrine(NE) and 5- hydroxytryptamine(5- HT) in serum in the two groups were observed and compared before and after treatment；Hamilton Depression Rating Scale(HAMD- 17)，Symptom Checklist- 90(SCL- 90) and Chinese medicine syndrome scores were compared between the two groups before and after treatment；the clinical effects and medication safety in the two groups were compared. Results：The total effective rate was 92.31% in the observation group and 76.00% in the control group， the difference being significant(P＜0.05). Before treatment， there was no significant difference being found in the comparison of levels of NE and 5- HT in serum between the two groups(P＞0.05). After treatment， levels of NE and 5- HT in the two groups were increased when compared with those before treatment(P＜0.05)，and the two levels in the observation group were higher than those in the control group(P＜0.05). Before treatment，there was no significant difference being found in the comparison of scores of HAMD- 17， SCL- 90 and Chinese medicine syndrome between the two groups(P＞0.05). After treatment，scores of HAMD- 17，SCL- 90 and Chinese medicine syndrome in the two groups were decreased when compared with those before treatment(P＜0.05)，and the above scores in the observation group were lower than those in the control group(P＜0.05). The incidence of adverse reactions was 1.92% in the observation group and 16.00% in the control group， the difference being significant(P＜0.05). Conclusion：In the treatment of depression，Zishen Kaiyu Anshen tang combined with Fluoxetine Hydrochloride Capsules has a better curative effect than the simple use of Fluoxetine Hydrochloride Capsules， and can effectively improve clinical symptoms， adjust the levels of serum NE and 5-HT，with fewer adverse reactions.