In this study, MMP-2 expression was decreased, PAI-1 and TIMP-2 expressions were increased in DN group compared to control group, and they were reversed by HACE or benazepril treatment, respectively; therefore it was concluded that upregulated PAI-1 and TIMP-2 inhibited the activity and expression of MMP-2 and then led to the ECM accumulation in streptozotocin-induced DN model, and HACE treatment inhibited ECM accumulation through regulating MMP-2, PAI-1, and TIMP-2 expressions. Here, SERPINE1 is linked to liver dysplastic nodule.