To explore effects of Tongxinluo on renal function and expression of MMP-9, TIMP-1, FN, Col-IV on diabetic nephropathy mice model, and investigate mechanism of action. Methods: Diabetic male KK-Ay mice were randomly divided into three groups: the model group(n=16),the Tongxinluo group(n=16) and the Western medicine group(n=16). A blank group was set up by male C57BL /6J (n=16) mice. After intervention with Tongxinluo and valsartan for 12 weeks, 24 h Urinary albumin excretion (24h UAER), fasting plasma glucose (FPG), serum creatinine (Scr), HbA1c, serum urea nitrogen(BUN) were examined. Expression of MMP-9,TIMP-1 were assessed by Realtime-Pcr and Western Blot. Expression of FN, Col-IV were assessed by immunofluorescence. Results: Compared with blank group, model group increased significantly for the following parameters: 24 h UAER, BUN, SCr, FPG, HbA1c, TIMP-1, FN, ColⅣ expression (P<0.05), and decreased significantly in MMP-9 expression. Compared with model group, both treatment group did not show significant changes in FPG and HbA1c (P>0.05), but had lower 24 h UAER, BUN and SCr (P<0.05), and Tongxinluo and valsartan can down- regulate TIMP-1,FN,ColⅣ expression and up-regulate the expression of MMP-9. Conclusion:Tongxinluo can decrease 24 UAER, protect renal function and inhibit extracellular matrix through regulating MMP-9/TIMP-1 expression.