The hepatoprotective effects of the fruits of Hovenia dulcis THUNB. on chemically or immunologically induced experimental liver injury models were examined. The methanol extract showed significant hepatoprotective activity against CCl4-toxicity in rats and D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. The methanol extract also significantly protected against CCl4-toxicity in primary cultured rat hepatocytes. Hepatoprotective activity-guided fractionation and chemical analysis led to the isolation of an active constituent, (+)-ampelopsin (1) from the methanol extract.