Aim To investigate the therapeutic effects of mangiferin on experimental diabetic nephropathy in rats,and explore the underlying mechanism. Methods The diabetic rats was induced by intraperitoneal injection with streptozotocin(STZ).The rats were randomly divided into five groups: the normal control group,the diabetic model group,the low(15 mg/(kg·d)),middle(30 mg/(kg·d)),high(60 mg/(kg·d)) doses of mangiferin therapy group.Renal weight,index number of kidney hypertrophy,fasting blood glucose and 24-hour urinary protein excretion were examined at 12 weeks.The structure of kidney was analyzed by light microscope.Immunohistochemistry and Western Blotting were used to detect the expression of transforming growing factor-β(TGF-β),matrix metalloproteinases-2(MMP-2),tissue inhibitors of matrix metalloproteinase-2(TIMP-2) in renal tissues. Results Compared with normal control group,the index number of kidney hypertrophy and 24-hour urinary protein were significantly up-regulated in the diabetic group;the protein expression of TGF-β and TIMP-2 were significantly up-regulated while MMP-2 was significantly decreased.Compared with the diabetic group,index number of kidney hypertrophy and 24-hour urinary protein were significantly decreased in mangiferin therapy groups(P><0.01);the protein expression of TGF-β and TIMP-2 were significantly decreased(P><0.05 or P><0.01),MMP-2 was significantly up-regulated(P><0.05 or P><0.01). Conclusion The expression of TGF-β,MMP-2 andTIMP-2 are related to diabetic nephropathy(DN),mangiferin has protective effect on kidney of diabetic rats through affecting the changes of above mentioned indexes.