Liver fatty acid binding protein has recently been shown to possess antioxidant properties but its role in liver disease, such as cholestasis, is not known. Since oxidative stress has been recognized as an important contributing factor in liver disease, we investigated the expression and antioxidative function of this protein using the bile-duct ligated model of cholestasis. Rats were divided into 3 groups: sham, bile-duct ligated and bile-duct ligated plus clofibrate. Animals were sacrificed at various time points after bile-duct ligation. RT-PCR and Western blot were used to analyze liver fatty acid binding protein expression. Cellular lipid peroxidation products were assessed by measuring thiobarbituric acid-reactive substances. Liver function was evaluated by measuring serum total bilirubin, alanine aminotransferase and ammonia. Liver fatty acid binding protein mRNA and protein levels were reduced to 51% and 20% of sham, respectively at 2 weeks following bile-duct ligation (p<0.05). The decreased liver fatty acid binding protein was associated with a statistical increase in hepatic lipid peroxidation products (224%) and decrease in hepatic function. Clofibrate treatment restored protein level and improved hepatic function. Clofibrate treatment also reduced hepatic lipid peroxidation products by 68% as compared with the bile-duct ligated group (p<0.05). Liver fatty acid binding protein likely has important antioxidant function during hepatocellular oxidative stress.