The effects of tannic acid (TA) supplementation (0·02 %, wt/wt) were compared with the effects of clofibrate (CF) supplementation (0·02 %, wt/wt) in apo E-deficient (apo E− / −) mice fed a AIN-76 semi-synthetic diet (normal diet) over 20 weeks. The mice were monitored for the modulation of hepatic mRNA expression and the activities of lipid-regulating enzymes. Both TA and CF supplementation lowered hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) activity and prevented atherosclerotic lesion formation in comparison with the control group. Hepatic carnitine palmitoyl transferase and β-oxidation activities were significantly higher in the TA and CF groups than in the control group. Both CF and TA supplementation resulted in significant decreases in hepatic HMGR mRNA levels in association with its enzyme activity. However, in contrast to CF supplementation, TA supplementation seemed to decrease the accumulation of hepatic lipids in the apo E− / − mice without increasing liver weight. These results suggest that the overall effect of TA is more desirable than CF for the alleviation of hepatic lipogenesis and atherogenesis in apo E− / − mice.