Objective: To investigate whether Qidan Shenluo Formula (QDSL) inhibits epithelial-mesenchymal transition (EMT) in podocyte by regulating the TGF-β1/Smads pathway, thereby ameliorating podocyte damage and glomerulosclerosis in diabetic kidney disease (DKD) rats. Methods: A DKD model was established in SD rats by high-fat diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). The established model rats were randomly divided into model group, QDSL high-dose group, low-dose group, rosiglitazone (Rosi) group, and normal control group according to body weight. After continuous oral administration for 6 weeks, blood glucose, urinary albumin-to-creatinine ratio (UACR), renal function, and blood lipids were measured. Immunohistochemistry, Western blot, and qRT-PCR were used to detect the expression of EMT-related markers (E-cadherin), nephrin, Col-I, desmin) and TGF-β1/Smads pathway proteins in renal tissue. Transmission electron microscopy was employed to observe changes in podocyte morphology and glomerular basement membrane (GBM). Hematoxylin and eosin (HE), pyronin A (PAS), and Masson staining were used to assess renal histopathological changes. Results: Compared with the model group, all QDSL dose groups and the rosiglitazone group significantly reduced blood glucose, UACR, and kidney weight ratio (KWR), improved renal function and blood lipids (P<0.05, P<0.01), and alleviated glomerulosclerosis, podocyte fusion, and GBM thickening. QDSL, particularly the high-dose group, demonstrated superior efficacy in improving the aforementioned indicators compared to the rosiglitazone group (P<0.05). Mechanistically, QDSL upregulated the expression of E-cadherin and nephrin, downregulated the expression of Col-I and desmin, and inhibited the levels of TGF-β1 and phosphorylated Smad2/3 (p-Smad2/3), while elevating the expression of Smad7 (P<0.05). The regulatory trends of EMT markers were consistent across all treatment groups but showed no statistically significant differences between groups (P>0.05). Conclusion: Qidan Shenluo Formula may inhibit podocyte EMT and reduce glomerular injury by modulating the TGF-β1/Smads signaling pathway, thereby delaying the progression of DKD. This provides an experimental basis for the therapeutic application of this formula in DKD.