Abstract: This study analyzed the effect of the Radix Bupleuri-Radix Paeoniae Alba herb pair on endogenous metabolites in rats with chronic unpredictable mild stress (CUMS)-induced depression by using LC-MS liver metabolomics. Rats were randomly divided into 5 groups:a normal control group, a CUMS model group, a venlafaxine-positive group, and a high-low dose group for the Radix Bupleuri-Radix Paeoniae Alba herb pair, with continuous modeling and administration over 28 days. The efficacy of Radix Bupleuri-Radix Paeoniae Alba herb pair was evaluated by measuring traditional pharmacodynamic indicators of depression (body weight, open field test, sucrose preference test and forced swimming test). Animal experimentation was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2016036). Liver metabolic profiles were obtained by the UHPLC-Q Exactive Orbitrap-MS metabolomics technique. The results show that the Radix Bupleuri-Radix Paeoniae Alba herb pair can significantly decrease depression-like behavior of rats in the CUMS model group. Increases in 25 depression-related metabolites were identified by LC-MS metabonomics, and the Radix Bupleuri-Radix Paeoniae Alba herb pair could significantly decrease 16 of them. Metabolic pathway analysis showed that D-glutamine and D-glutamate metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and glutathione metabolism were the main metabolic pathways altered by this herb pair in CUMS model rats.