Background: Liver failure is a worldwide health problem. Stem cells provide a great promise in regeneration of liver tissue. Objective:  Assessment of the role of apoptosis in the pathophysiology of liver failure and bone marrow derived mesenchymal stem cells (BM MSCs) effect on it. Materials and Methods: Twenty four adult male albino rats of local strain were chosen as an animal model for this study. They were divided into control, liver failure (LF) rats, LF rats received culture media and LF rats received BM MSCs.  Mesenchymal stem cells were separated from rat bone marrow, being identified by their morphology and immunophenotype (CD29, CD45 and CD90) by flow cytometry. BM MSCs were labeled with PKH26 dye before injection. LF was induced by oral administration of acetaminophen. At the end of the experiment (24 days), blood samples were obtained for estimation of serum alanine transferase (ALT) and aspartate transferase (AST). Animals were sacrificed and livers were obtained for measurement of BCL2 associated X protein (Bax), B-cell CLL/lymphoma 2 (BCL2) and transformation growth factor beta (TGFβ) gene expression in addition to histopathological examination of liver tissue. Results: BM MSCs were successfully separated from bone marrow, being identified as mesenchymal stem cells showing plastic adherence properties and fibroblastoid shape. The cells showed +ve expression of CD29 and CD90, -ve expression of CD45 proving that they were mesenchyml cells not hematopoitic cells. Acetaminophen showed significant increase in serum ALT and AST. There were significant increases of TGFβ and BAX gene expression in the liver tissue. There was significant decrease of BCL2 gene expression. BM MSCs showed significant decrease in serum ALT and AST, also there were significant decrease in TGFβ and BAX gene expression in the liver tissue in addition to significant increase in BCL2 gene expression. Histopathological examination revealed regeneration of the damaged liver tissue and restoration of normal architecture of liver tissue in BM MSCs-treated group in comparison with LF group. Conclusion: Apoptosis has important role in the pathophysiology of hepatic failure, and BM MSCs have significant role in its attenuation.