Objective To investigate the protective effects and possible mechanisms of berberine on the early change in renal hemorheology in diabetic rats.Methods The rat model of type 1 diebetes was established by intraperitoneal injection of streptozotocin.Fifty normal adult male Wistar rats were randomly devided into 5 groups: normal group,model group,captopril group(50 mg/kg/d),low dose berberine group(9.375 mg/kg/d) and high dose berberine group(28.125 mg/kg/d).The experimental rats were sacrificed at the end of the fourth week,and rat blood and urine were collected.The animal urine volume was measured and the ratio of kidney to body weight was calculated.Blood glucose,urine microalbumin,creatinine clearance rate,content of nitric oxide(NO) and activity of inducible nitric oxide synthase(iNOS) in renal tissue were measured,and the expression of iNOS in renal tissue was detected by immunohistochemistry.Renal pathological changes in all groups were examined by light microscopy.Results After 4 weeks,the values of urine volume,ratio of kidney to body weight,blood glucose,urine microalbumin,creatinine clearance rate,content of NO in renal tissue,activity of iNOS in renal tissue,iNOS expression,relative area of glomerular mesangium to glomerular basement membrane in model group were significantly higher than those of normal group(P<0.05).The above mentioned items in captopril and low dose berbrine groups were significantly decreased compared with those of model group(P<0.05).However,the difference was not significant compared with those of normal group(P>0.05).The observed items in the rats of high dose berberine group showed somehow partly improvement.Conclusion Berberine may exert protective effect on the injury of renal structure and function in diabetic rats.The mechanism may be related to the inhibition of iNOS expression and NO synthesis in the renal tissue.