reason the clinical use of this drug was restricted. The present study was intended to research the hepatoprotective impacts of bone marrow-derived mesenchymal stem cells against methotrexate, based on histological, immunohistochemical and ultrastructural parameters. Material & methods: Twenty four adult male albino rats were randomly divided into four experimental groups. Group I represented as control. Male adult albino rat received intramuscular (IM) injection of MTX (10 mg/ kg B wt.) once weekly for 6 weeks (group II) and others held for another 6 weeks without therapy then were sacrificed (group III). The rats received single dose of BM-MSC sintraperitoneal injection after induction of hepatic damage with MTX served as group IV. Light and electron microscopy were done to evaluate the histopathological changes. Results: Suppressive effect of BM-MSCs on activated hepatic stellate cells (HSC) was evaluated using immunohistochemical staining. Several histopathological changes were observed in liver cells of MTX‐treated animals; when compared with hepatocytes of control rats, had depletion of glycogen, distortion of hepatocyte and infiltration with some inflammatory cells. Conclusion: Our finding proved that of BM-MSCs injection after induction of hepatic damage with MTX induced therapeutic effects. Moreover, it reduced the hepatic lesions and significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of liver.