The purpose of this study is to determine the effect of dietary proteins and fats on the hepatic histological changes, membrane stability, and drug-metabolizing enzyme activities during chemically induced rat hepatocarcinogenesis. Weanling Sprague-Dawley rats were fed the diet containing 20% casein or soy protein isolate and 15% perilla or corn oil for 10 weeks. Hepatocarcinogensis was initiated with diethylnitrosamine(DEN), and the rats were fed diets containing 0.02% 2-acetylaminofluorene(AAF) followed by 0.05% phenobarbital (PB). The scores of histological changes were decreased in treated rats fed soy protein diet compared to those find casein diet. Liver weights were significantly increased by AAF and PB treatment in rats fed casein diets in both oil groups. Glucose 6-phosphatase(G6Pase) activities, an index of membrane stability, were significantly reduced by AAF and PB treatment in rats find casein diets, and were lower in casein diet compared to soy protein diet groups. Especially, the activities were the highest in the rats fed soy protein-perilla oil diet. Lipid peroxide values also were increased by AAF and PB treatment in rats fed casein diet. Aniline hydroxylase activities were not influenced by protein and fat sources. Glutathione-dependent enzyme activities were increased by AAF and PB treatment. Linoleic and arachidonic acid content were increased in rats fed corn oil diet, and linolenic and eicosapentaenoic acid contents were increased in rats fed perilla oil diet. Our results suggest that soy protein isolate inhibit the abnormal histological changes in liver, possibly by maintaining the membrane stability during chemically induced rat hepatocarcinogenesis. Soy protein may be protective against the hepatocarcinogenesis induced by chemical carcinogen.