To observe the effects of Tangshen Formula (TSF) treatment on renal fibrosis and explore its potential mechanism in db/db mice.Methods:Eight weeks old db/db and db/m mice were randomly divided into three subgroups,(db/m,db/db,db/db+TSF),and all mice were fed with a normal diet.After two weeks adaptation,mice were maintained on TSF treatment for 12 weeks and were then sacrificed under anesthesia after overnight fast.Animal urine and renal tissues samples were collected for further analyses.The kidneys were washed with cold PBS solution; one part of the renal tissue were stored in liquid nitrogen,and another deposited-80 ℃ directly for subsequent frozen sections; the rest of the kidney were fixed into the neutral formalin for pathological analysis.The renal fibrosis was detected by PAS and Masson staining.The renal expression of TGF-β1/Smad3 and its target genes were assessed by Western Blotting,real-time PCR,and IHC.Results:TSF diminished UACR of db/db mice.Histological analysis using PAS and Masson staining revealed the occurrence of mesangial matrix expansion and extracellular matrix deposition in the kidneys of db/db mice.The treatment with TSF significantly ameliorated these histological renal injuries in db/db mice.Western Blotting and real-time PCR analysis showed that expression levels of TGF-β1,Smad3,Collagen Ⅰ and Fibronectin were significantly downregulated in the db/db mice with TSF treatment.With TSF treatment,the expression levels of miRNA 21 was downregulated,but the expression levels of miRNA 29b was upregulated.Conclusion:TSF attenuated renal fibrosis in db/db mice,through suppression of TGF-β1/Smad3 pathway.