Abstract: Objective To establish a stable rat model of hyperuricemia. Methods By administering potassium oxonate alone or in combination with fructose or hypoxanthine, a hyperuricemia model was established with different administration times using various modeling method . The levels of serum uric acid, creatinine, urea nitrogen, xanthine oxidase (XO), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activity of hyperuricemia rats were measured. Pathological changes in the liver and kidney were observed. Protein expression of ATP-binding cassette subfamily G member 2 (ABCG2) were analyzed. Results Compared with the normal group, the levels of the serum uric acid, urea nitrogen, AST, and XO activity in rats administered potassium oxonate alone for 7 days were increased significantly (P< 0. 05), while the liver and kidney were slightly injured and kidney ABCG2 protein expression was decreased significantly (P<0. 05). Compared with the normal group, the level of serum uric acid in rats was increased significantly (P<0. 05), whereas the levels of creatinine, urea nitrogen, AST, ALT, and XO activity and kidney ABCG2 protein expression showed no significant changes (P>0. 05) in the group with 7 day of combined potassium oxonate and fructose administration. The levels of serum uric acid, urea nitrogen, and XO activity were increased significantly (P<0. 05) and the levels of AST and ALT activity showed no significant changes ( P> 0. 05) in the group with 14 days of potassium oxonate and fructose administration. There were no significant morphological changes in the liver and kidney of rats. Compared with the normal group, the levels of serum uric acid, creatinine, urea nitrogen, and AST, ALT, XO activity in rats with 7 days of potassium oxonate and hypoxanthine administration were increased significantly ( P< 0. 05 ). Kidney ABCG2 protein expression was decreased significantly (P< 0. 05) and the damage of the liver and kidneys was severe. Conclusions Potassium oxonate alone was suitable to establish a rat model of acute hyperuricemia with mild hepatic and renal injuries. Fructose combined with potassium oxonate may successfully establish a chronic hyperuricemia rat model with no significant effects on the liver or kidneys. Hypoxanthine combined with potassium oxonate successfully established an acute hyperuricemia rat model with severe hepatic and renal injuries.