OBJECTIVE: To observe the efficacy of Danggui Buxue decoction ((sic), DBD) on diabetic nephropathy-induced renal fibrosis in rats, and to study the possible mechanism. METHODS: Sixty male Goto Kakizaki (GK) rats were randomly assigned to the model group, gliquidone group, astragaloside IV group, and high-, medium- and low-doses DBD groups. After 8 weeks, changes in body weight, blood glucose, serum creatinine, serum urea nitrogen, and total cholesterol were observed. Changes in transforming growth factor-beta 1 (TGF-beta 1), Smad3, and Smad5 pathways and the expression of the fibrosis-related proteins collagen IV (col IV), alpha-smooth muscle actin (alpha-SMA), and vimentin were assessed. The degree of renal fibrosis was observed by immunohistochemistry and Mason staining. The expression of interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor (TNF-alpha), and C-reactive protein (CRP) in the kidneys was assessed using enzyme linked immunosorbent assay. RESULTS: Our experiments showed that DBD effectively reduced blood glucose, blood urea nitrogen, and creatinine levels after 8 weeks of administration, improved renal function in diabetic rats, alleviated renal fibrosis, and reduced the renal tissue levels of IL-6, IL-10, TNF-alpha, and CRP. Furthermore, DBD decreased the expression of TGF-beta 1, Smad3, col IV, alpha-SMA, and vimentin in renal tissues and increased the expression of Smad5. CONCLUSIONS: DBD ameliorates diabetic renal interstitial fibrosis by modulating the TGF-beta 1/Smads pathway. (c) 2023 JTCM. All rights reserved.