Abstract:Diabetic kidney disease (DKD) is a common and rapidly progressing microvascular complication in patients with diabetes, and it can develop to end-stage renal disease (ESRD) in severe cases. The current treatment mainly focuses on controlling blood sugar and blood pressure and using kidney - protecting drugs, which can delay the progression of the disease, but it is difficult to prevent its progression. In recent years, mesenchymal stem cells (MSCs) have emerged as a novel approach for DKD treatment due to their low immunogenicity, multipotent differentiation potential, and rich paracrine functions. Researches indicate that MSCs can exert renoprotective effects through a multi-target mechanism, including regulating macrophage polarization, inhibiting the transforming growth factor (TFG) -β/ small mother against decapentaplegic (Smad) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathways, upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway, maintaining mitochondrial function, restoring autophagy activity, and reversing the renal tubular epithelial-mesenchymal transition (EMT) process. In particular, MSCs-derived exosomes, characterized by stability, low immunogenicity, and easy storability, may offer a new direction for cell-free therapy. In animal models and early clinical studies, MSCs have demonstrated significant efficacy in improving proteinuria, alleviating renal tubulointerstitial fibrosis, and delaying renal function decline. Although the preliminary results are encouraging, further research and optimization are needed to address long - term safety, standardization of treatment protocols, and individualized delivery strategies. With the understanding of the mechanisms deepens and improvement of clinical techniques, MSCs and their derived exosomes hold promise for providing more precise and controllable treatment options for DKD.