Abstract: To explore the protective effect of Inonotus obliquus polysaccharide(IOP)on the kidneys of diabetic nephropathy mice,Streptozocin(STZ)induction combined with high-sugar and high-fat feed was used to establish a diabetic nephropathy mouse model. The test mice were randomly divided into a control group,a model control group,and a positive control group(metformin hydrochloride)and low,medium,and high-dose groups of Inonotus obliquus polysaccharides. After continuous intragastric administration of the mice for 4 weeks,the growth status of the mice was observed,the body weight of the mice was measured,the kidney index,renal function index,and the antioxidant capacity of the kidneys were determined and the pathological sections of the kidneys of the mice was observed. The results showed that the Inonotus obliquus polysaccharide dose group could alleviate the abnormal body weight,kidney value increased and kidney enlarged in diabetic nephropathy mice. The high-dose group could extremly significantly inhibit kidney swelling,repair kidney tissue damage(P<0.01),improve kidney oxidase activity(P<0.01),and inhibit malondialdehyde production. In conclusion,it could be concluded that the protective effect of obliquus polysaccharides on the kidneys of diabetic nephropathy mice was related to the polysaccharides inhibiting the peroxidative damage of mice and reducing the synthesis of lipid peroxidation.