Background: Novel therapies are urgently needed to address the rising incidence and prevalence of acute kidney injury (AKI) and chronic kidney disease (CKD). Mesenchymal stem cells (MSCs) can generate extracellular micro vesicles (EVs) with intrinsic protective or regenerative capacity. Objectives: Studying the possible role of EVs generated from bone marrow-derived mesenchymal stem cells (BM MSCs) in regeneration of kidney tissue in acetaminophen-induced renal failure (RF).  Patients and Methods: Twenty four adult male albino rats of a local strain were chosen as an animal model for this study. They were divided into 4 equal groups: control, RF, RF received culture media, and RF received MSCs-derived EVs. Renal failure (RF) was induced by oral administration of acetaminophen. At the end of the experiment (24 days), blood samples were obtained for serum creatinine, urea, malodialdehyde (MDA) and tumor necrosis factor alpha (TNF-α). Animals were sacrificed, and kidney tissue was obtained for histopathological examination and immunohistochemical examination for BAX protein expression, in addition to BCL2 gene expression by real time (RT) PCR. Results: There was a significant decrease in BCL2 gene expression in addition to significant increases in serum creatinine, urea, MDA and TNF-α in acetaminophen- treated group. There was an increased BAX protein expression by immunohistochemistry in acetaminophen- treated group. There were significant increase in BCL2 gene expression, and significant decreases in serum creatinine, urea, MDA and TNF-α in MSCs-derived EVs - treated group. There was a decrease in BAX protein expression by immunohistochemistry in MSCs derived EVs - treated group. Conclusion: BM MSCs-derived (EVs) have a role in regeneration of kidney tissue in acetaminophen-induced renal failure through antioxidant, anti-inflammatory and anti-apoptotic mechanisms.