Acute liver failure is impairment of liver functions,which may result from acute hepatocellular injury, that can produced by a variety of disorders. The present study was performed to evaluate the hepatoprotective effect of antioxidant vitamins (C and E), trace elements (zinc sulfate), calcium channel blocker (amlodipine), H2- blocker (cimetidine), organic nitrate (isosorbide dinitrate) and some medicinal plants (turmeric, licorice, black cumin, mastic tree, rhubarb) in an experimental model of acute liver failure. Seventy two local domestic rabbits were used in the present study, they were divided into 12 groups . One group was used as control in which carbon tetrachloride in a dose of 1.5 ml/kg was given orally to induce acute liver failure. Other groups were treated one hour before induction by one of the above mentioned agents for each group. Liver functions were assessed by estimating serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, also total serum bilirubin and total serum protein on two occasions; 24 and 72 hours after induction. Histopathological examination of the liver sections of each group was done at the end of experiment. Animals, were pretreated (one hour before CCl4 dosing) with vitamin C (250 mg/kg) or vitamin E (200 mg/kg) orally or a single dose of zinc sulfate (20 mg/kg) orally or using amlodipine besylate (1.25 mg/kg) orally or cimetidine (40 mg/kg) intraperitoneally or isosorbide dinitrate (1.42 mg/kg) orally as a single daily dose, the treatment continued for 2 successive days after the induction of failure. All these tested agents produced significant reduction in the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total serum bilirubin and significant elevation in the level of total serum protein (p<0.05) also they produced clear suppression of histopathological changes. Pretreatment (one hour before CCl4 dosing) with aqueous extracts of turmeric (1 gm/kg) or licorice (2 gm/kg) or mastic tree (1gm/kg) or rhubarb (0.2 gm/kg) or oil of black cumin (0.2 ml/kg) orally as a single daily dose continued for 2 days after induction of failure, resulted in significant decrease in the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total serum bilirubin, with increased level of total serum protein (p<0.05). Histopathological studies of the liver of different groups also support the hepatoprotective effects exhibited by those extracts.In conclusions, all the tested agents possess hepatoprotective activity by restoring the normal hepatic functions and potentiating the bio-defense system of the liver against oxidative damage produced by CCl4 administration.