Acetaminophen is a commonly used analgesic and antipyretic drug that could exert acute and chronic liver cell failure. Mesenchymal stem cell therapy offers advantages for tissue repair and regeneration in clinical research. To elucidate the therapeutic effect of stem cells on different doses of acetaminophen-induced hepatotoxicity in adult male albino rats, sixty adult male albino rats weighing 170-230 g were divided into six groups: Group I (Normal control) were injected intraperitoneally with isotonic saline three times over one week. Group II receive a single intravenous injection of MSC. Group III and IV: were injected intraperitoneally three times over one week by acetaminophen at a dose of 300 mg/kg (Group III) and 600 mg/kg (Group IV) respectively. Group V and VI were injected with acetaminophen 300 mg/kg (Group IV) and 600 mg/kg (Group V), followed in both groups by a single intravenous injection of MSC 24 hours after the last dose of acetaminophen. Blood samples were collected from the tail vein of the rats for assessment of biochemical markers of liver, then they were anaesthetized and sacrificed. Liver homogenate was assessed for Malondialdehyde (MDA) and Super Oxide Dismutase (SOD). Liver specimens were subjected to histopathological examination and ultrastructural study. Statistical analysis was done for the results of hepatic biomarkers. Examination of specimens of group III and IV revealed disturbed hepatic architecture, nuclear and cytoplasmic degeneration and increased serum liver enzymes compared to the control group I. However, MSC markedly ameliorated these histological and laboratory alterations in both group V and VI. It could be concluded that stem cells had a beneficial role in treatment of hepatotoxicity exerted by acetaminophen administration in adult male albino rats