Aim To investigate the effect of berberine on the expression of nephrin, podocin and intergrinα3β1 in diabetic nephropathy ( DN ) rat model, and further probe in to the renoprotective effects of berber-ine and its potential mechanisms. Methods The rat model of DN was induced by intraperitoneal injection of streptozotocin ( STZ ) after fed with high-sugar and high-fat diet for six weeks. The rats were assigned into 6 groups randomly: normal control group, DN model group, BBR (50,100 and 200 mg·kg-1 ) treatment group and enalaprilat positive control group ( 1 mg · kg-1 ) . The distribution and expression of kidney podocyte related proteins nephrin, podocin and interg-rinα3β1 were detected by immunohistochemical meth-od following electron microscopy observation ( × 1000 ) and high magnification observation( × 400) and West-ern blot. Results The podocyte related protein neph-rin, podocin and intergrin α3β1 were mainly distribu-ted in podocyte, but slightly different. Compared with normal control group, the expresion of podocyte related protein nephrin, podocin and intergrin α3β1 was de-creased obviously; compared with model group, BBR (100 and 200 mg·kg-1 ) treatment group could sig-nificantly suppress the abnormalities of pathological changes of the kidney and upregulate the expression levels of podocyte specific protein nephrin, podocin and intergrin α3β1 in the kidney of diabetic rats with nephropathy. Conclusions Berberine could alleviate the abnormalities of kidney pathological changes and proteinuria production in the DN model rats, which may be related to the upregulation of the expression of the podocyte proteins nephrin, podocin and intergrinα3β1.