Phillygenin is a bioactive intergradient in Osmanthus fragrans, a well-known food additive and Chinese traditional medicine. This study was to investigate the hepatoprotective effects and pharmacokinetics of phillygenin. The hepatoprotective effect of phillygenin was assessed in carbon tetrachloride- (CCl4-) intoxicated mice by monitoring levels of serum and tissue biomarkers. The pharmacokinetics of phillygenin was evaluated in the mouse after oral (po, 24 mg / kg) or intravenous (iv, 12 mg/kg) administration. Results showed that phillygenin has a great hepatoprotective effect on CCl4-induced liver injury in mice owing to its antioxidant activity and inhibition on cytochrome P450 2E1(CYP2E1). After oral administration, phillygenin was efficiently absorbed with the oral bioavailability of 56.4%. Two metabolites, hydroxylated and dimethylated phillygenin, were identified in mouse urine. These results suggested that phillygenin could be explored as new and potential natural antioxidants and hepatoprotective agents.