Objective Establish a reasonable and stable rat model of uric acid nephropathy to provide a pathological model for screening, research, and treatment of uric acid nephropathy. Methods Experimental rats were randomly divided into three model groups and a control group. Model mice were administrated orally with 750 mg / kg oteracil potassium combined with 150 mg / kg low dose uric acid (M-A), 750 mg / kg oteracil potassium combined with 300 mg / kg medium dose uric acid (M-B), or 750 mg / kg oteracil potassium combined with 600 mg / kg high dose uric acid (M- B). After continuous intragastric administration for 4 weeks, changes in blood uric acid, blood creatinine, urea nitrogen, triglycerides, cholesterol and other indicators as well as pathological changes of the kidneys were observed for 4 weeks. Results Compared with the control group, the serum uric acid of the three model groups was significantly higher (P< 0.01, P<0.05, P<0.05), serum creatinine of the M-B and M-C groups was increased significantly (P<0.05, P<0. 01), triglycerides of the M-B group were significantly lower (P<0.05). Renal pathology scores of M-B and M-C groups were significantly higher those of the control group (P<0.01). Masson staining of morphology showed that, in comparison with the control group, kidney damage was more obvious in the three model groups ( P< 0.05, P< 0.01, P< 0.01 ). Immunohistochemical staining of inflammation marker CD68 showed that, compared with the control group, its expression was increased of in three model groups (P<0. 05, P<0. 01, P<0. 01). Expression of epithelial cell marker E-Cadherin was significantly reduced in M-B and M-C groups in comparison with to the control group ( P< 0.01 ). Expression of myofibroblast marker protein α-SMA was increased the three model groups compared with the control group (P<0.05, P< 0.01, P<0.01). Conclusions Oteracil potassium (750 mg / kg) combined with the middle dose of uric acid (300 mg / kg) is ideal to establish a rat model of uric acid nephropathy.