The purpose of this study was to investigate possible beneficial effects of Panax ginseng (PG) on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in rats. CCl4 challenge elevated serum enzyme activities of liver and some biochemical parameters, but these effects were prevented by the pretreatment of rats with PG. Histologically, a great amount of mononuclear cells infiltration, necrotic cells and few fibroblasts were observed in liver of CCl4 group. Also, CD68(+) and caspase-3 staining cells were diffused in both lobular and portal areas. However, PG pretreatment had a little influence on the number of caspase-3 immunpositive staining cells in the liver, but CD68(+) staining areas were significantly decreased in the PG + CCl4 when compared to CCl4 group. We conclude that PG treatment may play a protective role by enhancing liver enzyme activities and recovering biochemical parameters, and improving the changes in histological structure against CCl4-induced liver damages in rats. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.