Objective To investigate the changes in endogenous metabolites in a rat model of depression and the modulatory effect of Baihe Zhimu decoction(BZD) on the abnormal metabolites through a metabolomic approach. Methods Forty rats were randomly divided into normal control group

depression model group

fluoxetine treatment group and BZD treatment group. In all but the control group

rat models of depression were established by keeping the rats in separate cages combined with exposure to chronic unpredictable mild stress. A metabolomic approach was used to identify the endogenous metabolites and metabolic pathways that were related to the antidepressive effects of BZD. Results BZD could significantly increase the body weight

sucrose preference and behavioral scores in the rat models of depression(P<0.05). BZD treatment resulted in the recovery of normal levels for 23 metabolites that showed abnormal serum levels in the depressive rats

and these metabolites were associated with fatty acid amide metabolism

phenylalanine metabolism

glycine metabolism and lipid metabolism. By comparison

fluoxetine treatment only restored the normal levels for 17 abnormal metabolites

which were related with glycine metabolism and lipid metabolism. Conclusion BZD can modulate more metabolic pathways than fluoxetine for treatment of depression.