Here, we examined the therapeutic potential of AANG on T2D and T2DN and identified its safe dosage window and optimal combination ratio that effectively protected db/db mice against T2D and T2DN development by blocking both NF-kB-mediated renal inflammation and Smad3-mediated renal fibrosis in vitro and in vivo. This evidence concerns the gene SMAD3 and type 2 diabetes mellitus.