To investigate the effect of gentiopicroside on fructose-induced hyperuricemia in mice.Methods:The hyperuricmia KM mice were induced by feeding water containing 10% fructose for consecutive 12 weeks.During the period from 9th week to 12th week，mice from allopurinol group and gentiopicroside groups(80，40，20 mg/kg) received allopurinol and gentiopicroside，respectively by intragastric administration once a day for 4 weeks.The blood was collected after the last administration，to detect glutamic pyruvic transaminase(GPT)，glutamic oxaloacetic transaminase(GOT)，uric acid(UA)，creatinine(Cr) and blood urea nitrogen(BUN) in serum.H&E staining was performed to observe the changes in liver and kidney tissues.Superoxide dismutase(SOD)，malondialdehyde(MDA)，tumor necrosis factor-α(TNF-α) and interleukin 6(IL-6) in kidney tissues were measured by enzyme-linked immunosorbent assay(ELISA)，and the activity and expression of XOD in liver were tested by colorimetry and Western Blotting.Results:Compared with the model group，the mice in gentiopicroside groups showed a decrease in serum GPT，GOT，UA，Cr and BUN(P<0.01)，with improvement in pathological changes of liver and kidney.The SOD in kidney were increased，whereas MDA，TNF-α and IL-6 were lowered(P<0.01).Moreover，gentiopicroside reduced the activity and protein expression of XOD in liver(P<0.01 or P<0.05).Conclusion:Gentiopicroside down-regulates UA in the fructose-induced hyperuricemia mice by modulating the activity and the expression of XOD，thereby alleviating oxidative stress，and inflammation and protecting the kidney.