To study the antidepressant effects of Peiyuan Jieyu Decoction and the regulatory mechanism of the tryptophan-kynurenine (TRY-KYN) metabolic pathway.Methods:The rat model of depression induced by intraperitoneal injection hydrocortisone was built.The symptoms of depression were observed by sucrose preference experiment.The contents of tryptophane，kynurenine，kynurenic acid and quinaldinic acid in brain tissue were detected by HPLC-MS/MS technique.The mRNA expression levels of TDO in liver tissue，IDO and 5-HT1A in brain tissue were detected by using real-time PCR.Results:After 21 days' acute stress，the preference in sucrose was reduced.The ratio of KYN/TRY and the content of QUIN were increased.The content of KA was decreased.The expression of TDO mRNA increased and the expression of 5-HT1A mRNA decreased (P<0.05).The Fluoxetine group，Tiansi decoction group，Sini decoction group，high dose and middle dose of Peiyuan Jieyu decoction group could improve the preference in sucrose preference experiment (P<0.05).Each treatment group could obviously reduce the ratio of KYN/TRY (P<0.05).Tiansi decoction and middle dose of Peiyuan Jieyu decoction could significantly improve the content of KA，and decrease the content of QUIN P<0.05).Tiansi decoction could obviously decrease the expression of TDO mRNA in liver and the expression of IDO mRNA in hippocampus (P<0.05).Sini decoction，middle dose and high dose of Peiyuan Jieyu decoction could increase the expression of 5-HT1A mRNA in hippocampus (P<0.05).Conclusion:Traditional Chinese medicine groups have antidepressant effects.Its mechanism may be connected with reducing the expression of the key enzyme mRNA in TRY-KYN metabolic pathway，improving the neuron protective effect by reducing neurotoxic metabolites and increasing neuroprotective metabolites，and increasing the expression of 5-HT1A.