Abstract: OBJECTIVE To investigate the changes of endogenous metabolites before and after treatment of ulcerative colitis in mice with Baitouweng Decoction， to find metabolic biomarkers related to the treatment of ulcerative colitis， and to explore the regulation and the possible mechanisms of Baitouweng Decoction on ulcerative colitis model. METHODS The mouse model of ulcerative colitis was constructed by DSS. The serum samples of each group were determined by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to screen for differential metabolites. RESULTS The serum samples of the control group， the model group and the Baitouweng Decoction group could be well distinguished. A total of six potential biomarkers were identified， and the endogenous metabolites of the mice were varying degrees of callbacks after the administration of Baitouweng Decoction. CONCLUSION Baitouweng Decoction could restore the abnormal metabolism of DSS-induced ulcerated mice， and its therapeutic effect may be related to the regulation of six metabolites and three related metabolic pathways.