Objective To establish a rat model of hyperuricemic nephropathy (HN) using a multifactorial induction method of potassium oxazinate combined with adenine and yeast feed, and to observe the intervention effect of Qiling granules (QLG). Methods Fifty-eight SPF grade male SD rats were selected, and ten rats were randomly selected as the normal control 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 model control group, QLG low and high dose groups, and positive control group using a stratified randomization method, with ten rats in each group. 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 rats, and 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 WB methods. Results Compared with the normal control group, the serum levels of UA, CREA, BUN, TC, and TG, as well as liver XOD and ADA activities, were significantly increased in model control Group (P<0.01). The renal tissue of rats shows significant pathological changes. The positive area of urate in renal tubules 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 model control group, the serum UA levels, liver XOD, ADA activity, and renal VCAM-1 protein expression of rats in each treatment group were significantly reduced (P<0.01, P<0.05). The serum CREA, BUN levels, and renal TGF-β protein expression of rats in the low-dose QLG group were also significantly reduced (P<0.05, P<0.01). The serum CREA, BUN levels, and renal GLUT9 protein expression of rats in the high-dose QLG group were also significantly reduced (P<0.01, P<0.05), and the urate deposition and renal injury caused by them in each treatment group were reduced to varying degrees, but there was no significant difference (P>0.05). Conclusion A stable HN rat model can be induced by gavage of potassium oxyzinate and adenine in combination with yeast feed to rats; QLG can effectively treat HN by improving UA metabolic disorders, reducing renal inflammation and urate deposition, as well as causing renal damage in HN model rats. Its mechanism of action is related to reducing serum UA, CREA, BUN, TG levels, liver XOD and ADA activities, as well as the expression of GLUT9, OAT1, VCAM-1, and TGF-β proteins in the kidneys.