Abstract: Objective Residual symptoms are principal elements of symptoms recurrence and diseases relapse in the treatment of depressive disorder, the aim of this article is to explore effects of acupuncture of soothing-liver and nourishingheart method combined with venlafaxine on residual symptoms, clinical recovery and serum monoamine neurotransmitter level in depressive disorder patients. Methods Total 91 depressive disorder patients were randomly divided into drug group (only venlafaxine) and acupuncture-drug group (acupuncture combined with venlafaxine), all of them were treated for 8 consecutive weeks. Hamilton Depression Scale (HAMD) was used to assess residual symptoms and clinical recovery after the treatment, the level of serum monoamine neurotransmitter was tested before and after the treatment. Residual symptoms, clinical recovery and serum 5-HT, NE and DA levels in the two groups were analyzed statistically by χ² test, independent sample t test and one-way analysis of variance (ANOVA). Results HAMD total score, anxiety/somatization, weight, cognitive disorder, retardation and sleep disorder of drug group and acupuncture-drug group decreased after the treatment (P < 0. 01). As compare with the drug group, HAMD total score, anxiety/somatization and sleep disorder factor scores after the treatment in the acupuncture-drug group were lower (P < 0. 01 or P < 0. 05), however, the clinical recovery rate was higher (P < 0. 05). After the treatment, levels of 5-HT, NE and DA of both groups were decreased (P < 0. 01).When compare with drug group, levels of 5-HT, NE and DA after the treatment in the acupuncture-drug group were higher (P < 0. 01). Conclusion Acupuncture of soothing-liver and nourishing-heart method combined with venlafaxine for depressive disorder can promote the remission of residual symptoms and improve clinical recovery rate, the mechanism may relate to the elevated serum levels of 5-HT, NE and DA.