Abstract: We studied the effects of dietary fat composition on the activities of the microsomal ethanol oxidizing system (MEOS), paranitrophenol hydroxylase (PH) activity and ethanol-inducible cytochrome P450 isozymes (CYP2E1 and CYP2B1) in the liver of rats to determine the role of this ethanol metabolizing pathway in the pathogenesis of alcoholic liver disease (ALD). Wistar male rats were pair-fed a liquid diet, containing either tallow (TF) or corn oil (CF) as the fat component, and ethanol or an isocaloric amount of dextrose, through an implanted intragastric cannula. Liver pathology of rats fed ethanol (CF-ALC) and CF diet showed severe fatty change whereas the rats fed TF-alcohol and the TF and CF controls did not. MEOS activity of the CF-ALC group was 8 times of that in the CF-CTL group (P < 0.01). In TF-ALC rats, MEOS activity was increased to 2.6 times compared to that of TF-CTL (P< 0.01). ApoCYP2E1 in CF-ALC and TF-ALC were 818 ± 63 and 433 ± 17 pmol/mg protein, respectively, and these values were significantly higher when compared with those of the pair-fed controls (P< 0.005). In contrast, apoCYP2B1 was increased to an equal degree in both CF-ALC and TF-ALC. When PH-activity was measured, the level of activity on TF-ALC rats did not differ from that of CF-ALC rats. Thus, ethanol-induction of apoCYP2Bl (2 x) and PH (6–8 x) were the same for CF and TF (2 x); but not for apoCYP2E1 (21 and 8 x, respectively) and MEOS activity (8 and 2.6 x, respectively). These results indicate that the dietary effect on the expression of CYP2E1 correlates with the induction of centrilobular liver damage seen in the corn oil fed rats. The centrilobular distribution of this isozyme also correlates with the site of liver cell injury further suggesting a pathogenic link to alcohol-induced cell injury.