Objective To establish a rat model of hyperuricemic nephropathy ( HN) using a multifactorial induction method of potassium oxazinate combined with adenine and yeast feed to observe the intervention effect of Qiling granules (QLG) . Methods Fifty-eight SPF-grade male SD rats were selected, and 10 rats were randomly allocated to the normal control (NC) group. The remaining rats were induced by multiple factors to establish HN rat models. After 2 weeks of modeling, submandibular blood samples were taken to detect serum UA, CREA, BUN, TG, and TC. Forty HN rats with bleeding clearance UA and body weight close to the mean were selected. They were randomly divided into a model ( M) group, QLG low dose (QLG-L) groups, QLG high dose (QLG-H) group, and a positive control ( PC) group, with 10 rats in each group, using a stratified randomization method. Each group was given corresponding drugs by gavage daily, and after continuous administration for 4 weeks, submandibular blood samples were taken to detect serum UA, CREA, BUN, TG, and TC. After euthanasia of the rats, liver tissue was taken to detect XOD and ADA activity. Renal tissue was taken for HE and Gomori hexamine silver staining, and the protein expression of GLUT9, OAT1, VCAM-1, and TGF-β in the kidneys was observed using immunohistochemistry and Western blot method. Results Compared with the NC group, the M group’ s serum levels of UA, CREA, BUN, TC, and TG, as well as liver XOD and ADA activities, were significantly increased (P<0. 01) . The renal tissue of the model rats showed significant pathological changes. The area of renal tubules positive for urate and the expression of GLUT9, VCAM-1, and TGF-β proteins in the kidneys were significantly increased (P<0. 01, P<0. 05) ,while the expression of OAT1 was significantly reduced ( P<0. 01) . Compared with the M group, each treatment group showed significantly reduced serum UA levels, liver XOD, ADA activity, and renal VCAM-1 protein expression (P<0. 01, P<0. 05) . The serum CREA and BUN levels and renal TGF-β protein expression of rats in the QLGL group were significantly reduced ( P<0. 05, P<0. 01) . The serum CREA and BUN levels and renal GLUT9 protein expression of rats in the QLG-H group were also significantly reduced (P<0. 01, P<0. 05) . The urate deposition and renal injury caused by each treatment were reduced to varying degrees, but there were no significant differences among groups (P>0. 05 ) . Conclusions A stable HN rat model can be induced by gavage of potassium oxyzinate and adenine in combination with yeast feed. QLG can effectively treat HN by improving UA metabolic disorders, reducing the renal inflammation and urate deposition that cause renal damage in HN model rats. Its mechanism of action is related to a reduction in serum UA, CREA, BUN, and TG levels; liver XOD and ADA activities; and the expression of GLUT9,OAT1, VCAM-1, and TGF-β proteins in the kidneys.