Objective To establish a rat model of diabetic nephropathy, with similar laboratory test results and clinical symptoms in patients with diabetic nephropathy and to evaluate the stability of this animal model. Methods Sixty-six healthy male Spraque-Dawley rats were used in this study. Except those in the normal group,all rat models of diabetic nephropathy were established by unilateral nephrectomy and tail vein injection of streptozotocin (STZ).Dynamic changes of parameters such as body weight, water intake, urine volume, urinary albumin, 24 h urinary protein content, blood glucose level, glycosylated hemoglobin, blood lipid, serum creatinine and urea nitrogen were observed, and renal pathology was also examined to evaluate the success and stability of this rat models. Results The blood sugar, water intake and urine volume were higher than those in the normal group, and body weight loss was observed at 3 days to 16 weeks after STZ administration. The model group rats showed early diabetic nephropathy in 4 weeks, the urinary albumin, 24 h urinary protein and glycosylated hemoglobin were significantly increased than those in the normal group, and the blood lipid, urea nitrogen and creatinine also showed abnormality. The condition was gradually worsening with the extension of time. Conclusion Unilateral nephrectomy and tail vein injection of streptozotocin (STZ) induced nephropathy in rats is in accordance with early diabetic nephropathy in humans of both laboratory test results and clinical symptoms. The rat models at 4 to 16 weeks after modeling are in accordance with clinical nephropathy Mogensen stage Ⅲ. The severity of disease of the rat models is along with the disease course, and is stable and suitable for studies on drug pharmacodynamic evaluation and basic clinical studies on diabetic nephropathy.