Introduction: Cimetidine (CIM) is used for treatment of ulcers and hyperacidity. This drug also is used as inhibitor of the microsomal monooxygenase system activity. Carbon tetrachloride (CCL4) is widley used as an industrial solvent as well as a cleaning agent. This chemical is biotransformed by cytochrome p450 to trichloromenthl radial, which binds irreversible to the essential macromolucles induced toxicity. The purpose of the present study was to investigate the effect of CIM on CCL4 produced liver injury in the rats.Methods: The animals were given 120 mg/kg (ip) of CIM. Control rats were received vehicle only.The animals were given CCl4 at doses of 0, 0.5, 1, 1.5 or 2 mg/kg 12 h later. The rats were killed with over dose of sodium pentobarbital 24 h later. The blood was collected to determine of ALT, AST, ALP changes.The liver tissues were removed, fixed and processed to light microscopy, using H& E staining method.Results: The results of this study revealed that CCL4 had induced a dose- dependent injury in the liver of rat tissues. Statistical analysis showed a significant increase in all of biochemical parameters in CCl4-treated rats when compared to the control groups (P<0.05). The findings of this study also showed that CIM had no adverse effect on the rat liver and this agent protected cells against CCl4 toxicity.Conclusion: The results of this study support the view that CIM has ability to reduce CCl4 –induced hepatotoxicity. Our findings suggest that in the presence of CIM, parent form of CCl4 could induce more adverse effects than its toxic reactive metabolite (s).