OBJECTIVE: To investigate how compound Sophorae decoction(CSD) works on rats' models of ulcerative colitis(UC) induced by 2,4,6-trinitrobenzenesulfonic acid solution(TNBS) by metabolomics studies of colon, liver, and kidney tissue extracts.METHODS: Rats with UC induced by TNBS enema were used as models in this study. Metabolic profiles of the three tissues were analyzed and pathway analysis of biomarkers was performed after CSD administration and further integration of metabolic networks.RESULTS: Thirteen biomarkers were screened from colon, liver, and kidney tissue extracts, and the levels of these substances were up-or down-regulated in the model group, but their levels were reversed after CSD administration. These biomarkers were mainly related to Phenylalanine, tyrosine and tryptophan biosynthesis, Phenylalanine metabolism, Glutathione metabolism, Arachidonic acid metabolism, Nicotinate and nicotinamide metabolism,Alanine, aspartate and glutamate metabolism.CONCLUSION: CSD could significantly ameliorate the symptoms of UC by regulating multiple metabolic pathways.