Objective To observe the effect of breviscapine Yishen Granule on TGF-Smad transduction pathway in diabetic nephropathy（DN） rats， and to explore its preventive and therapeutic effects on DN. Methods The 90 male SD rats were randomly divided into normal group（group A）， model group（group B）， hydrochloric acid Benner Pury group（group C）， and the Breviscapine Yishen granules’s group were divided into low， middle and high dose group（group C， D， E）. While， with streptozotocin（STZ）intraperitoneal injection of 55mg/kg to set up DN model. After given different experimental factors intervention， observed The levels of cystatin C（CysC）， serum creatinine（Scr）， blood urea nitrogen（BUN） and urinary protein/urine creatinine（Up/Ucr） by biochemical detection. And observed the expression of TGF-beta 1， Smad 2， Smad 7， collagen type IV and fibronectin（FN） in renal tissue of rat models was detected by immunohistochemistry. Results The levels of of E， F Up/Ucr， Cys C， BUN group was lower than that of B group（P<0.05 or P<0.01）； The expression of TGF-beta 1， Smad 2， type IV collagen， FN protein in group E and F renal tissue was significantly lower than that of group B（P<0.01）， lower than group C and D（P<0.05）， the expression of Smad 7 protein was higher than group B（P<0.05）， more than group C and D（P<0.05）. Conclusion Breviscapine Yishen granule can inhibit the activation of TGF-Smad signaling pathway in renal tissue of diabetic nephropathy rats， and reduce the expressions of type IV collagen and FN protein in tissues. The effect of medium and high dose group was better than that of low dose group and Benner Pury hydrochloride group.