Abstract: To explore the role and mechanism of selenium protein ( Se-76P) on streptozocin-induced diabeticnephropathy in mice.Diabetic nephropathy model were prepared with streptozocin ( 40 mg/kg) by intraperitoneal injection in male C57BL/6J male mice.60 mice were divided into six groups, normal control group ( group Ⅰ) , model of diabetic nephropathy group ( groupⅡ) , model + low-dose Se-76 P group ( group Ⅲ) , model + middle-dose Se-76 P group ( group Ⅳ) , model + high dose Se-76 P group ( group Ⅴ) and insulin treatment group ( group Ⅵ) . Both groups of mice were administrated by subcutaneous injection way, group Ⅰ and group Ⅱ was given saline, group Ⅲ, Ⅳ and Ⅴ were given low ( 20 μmol/kg) , middle ( 40 μmol/kg) and high ( 60 μmol/kg) concentration of Se-76 P protein, group Ⅵ was given insulin, 5 U/kg·d. All groups were treated for 4weeks, and body weights were measured every week. After the experiment, blood glucose, serum creatinine ( SCr) and urea nitrogen ( BUN) levels were measured in serum. The urine creatinine ( UCr) and microalbuminuria ( MAU) levels were detected and the creatinine clearance ( CCr) was calculated, renal tissue malondialdehyde ( MDA) , superoxide dismutase ( SOD) and glutathione peroxidase ( GPx) levels were also detected.Compared with model group, fasting blood sugar were decreased in Se-76 P administrated groups, the levels of SCr, BUN, UCr, MAU and CCr were significantly decreased ( p < 0.01 or 0.05) .The MDA level was decreased in kidney tissues significantly ( p < 0.01) , SOD and GPx activity were increased significantly ( p < 0.01 or p < 0.05) . Se-76 P may improve renal function in STZ-induced diabetic nephropathy mice by increasing SOD and GPx activities, enhancing antioxidant levels.