Abstract: OBJECTIVE To research the effect and mechanism of fermentation of Astragalus membranaceus on endogenous metabolites in hyperuricemia model rats using serum UHPLC-HRMS. METHODS The SD rats were randomly divided into different groups, including blank group, model group, benzbromarone group(20 mg·kg^-1), as well as fermentation of Astragalus membranaceus high-dose(3 g·kg^-1) and low-dose group(1.5 g·kg^-1). Model group and each treatment group were disposed with 300 mg·kg^-1 oxonic acid potassium to establish hyperuricemia models. At the time of 1 h after modeling, rats in each treatment group were given corresponding drugs for intervention. Collected rat serum after 14 d. The serum of different groups were collected for endogenous metabolites research using UHPLC-HRMS. After multivariate statistical analysis, the different metabolites and metabolic pathways were selected. RESULTS The hyperuricemia rat modes were successfully established by oxonic acid potassium 14 d, and fermentation of Astragalus membranaceus showed good uric acid reducing effect. Compared with the blank group, 17 potential biomarkers associated with hyperuricemia were found in the model group. Among them, 9 potential biomarkers were significantly recalled by fermentation of Astragalus membranaceus. It mainly involved sphingolipid metabolism, pyrimidine metabolism, tryptophan metabolism, pantothenic acid and CoA biosynthesis, glycine, serine and threonine metabolism and other pathway. CONCLUSION This study can provide a basis for revealing the mechanism of reducing uric acid by fermentation of Astragalus membranaceus, and lay a foundation for the further development and utilization of Astragalus.