Chronic kidney disease (CKD), a global health concern, is highly prevalent among adults. Presently, there are limited therapeutic options to restore kidney function. This study aimed to inves tigate the therapeutic potential of breast milk mesenchymal stem cells (Br-MSCs) and their derived exosomes in CKD. Eighty adult male Sprague Dawley rats were randomly assigned to one of six groups, including control, nephropathy, nephropathy + conditioned media (CM), nephropathy + Br-MSCs, nephropathy + Br-MSCs, nephropathy + Br-MSCs derived exosomes (Br MSCs-EXOs), and nephropathy + Br-MSCs + Br-MSCs EXOs. Before administration, Br-MSCs and Br-MSCs-EXOs were isolated, identified, and labeled with PKH-26. SOX2, Nanog, and OCT3/4expression levels in Br-MSCs and miR-29b, miR-181, and Let-7b in both Br-MSCs and Br MSCs-EXOs were assayed. Twelve weeks after transplantation, renal function tests, oxidative stress, expression of the long non-coding RNA SNHG-7, autophagy, fibrosis, and ex pression of profibrotic miR-34a and antifibrotic miR-29b, miR-181, and Let-7b were measured in renal tissues. Immunohistochemical analysis for renal Beclin-1, LC3-II, and P62, Masson trichome staining, and histopathological examination of kidney tissues were also performed. The results showed that Br-MSCs expressed SOX2, Nanog, and OCT3/4, while both Br-MSCs and Br-MSCs-EXOs expressed antifibrotic miR-181, miR-29b, and Let-7b, with higher expression levels in exosomes than in Br-MSCs. Interestingly, the administration of Br-MSCs + EXOs, EXOs, and Br-MSCs improved renal function tests, reduced renal oxidative stress, upregulated the renal expression of SNHG-7, AMPK, ULK-1, Beclin-1, LC3, miR-29b, miR 181, Let-7b, and Smad-7, downregulated the renal expression of miR-34a, AKT, mTOR,P62, TGF-β, Smad-3, and Coli-1, and ameliorated renal pathology. Thus, Br-MSCs and/or their derived exosomes appear to reduce adenine-induced renal damage by secreting antifibrotic microRNAs and potentiate renal autophagy by modulating SNHG-7 expression.