SummaryOxidized frying oil (OFO) activates peroxisome proliferator-activated receptor a (PPAR a) in vitro and in vivo. As most PPARa activators are also peroxisome proliferators (PP), this study was aimed at exploring whether OFO induces peroxisome proliferation in the liver of rats. Four groups of male weanling Sprague-Dawley rats were fed the following diets for 6 wk: a basal diet containing 5g/100 g fresh soybean oil (LSB), high-fat diets con taining 20g/100g of fresh soybean oil (HSB as a control), OFO (HO) or fish oil (HF, as a pos itive control). Hepatomegaly and peroxisome proliferation in the liver of the HO group of rats were higher than those of the HF group. In addition, the acyl-CoA oxidase (ACO) activity, as well as cytochrome P450 4A (CYP4A) protein content in the livers of the HO group were 6 fold those of the HSB group, but were 2.5 fold in those of the HF group. These results indi cated that dietary OFO induced typical responses to PPARa signaling. Moreover, as a dietary source, the OFO prepared under our frying conditions appears to be a more potent peroxi some proliferator than fish oil. Key Words oxidized frying oil, fish oil, acyl-CoA oxidase, cytochrome P450 4A, peroxi some proliferation Fat samples oxidized under more realistic cooking practices (frying) as part of a nutritional balanced diet gave rise to mild symptoms, such as: less body weight gain and feed intake, and enlargement of liver and kid ney, in long term animal studies (1, 2). The modest bio logical effect could be attributed to a decreased diges tion and absorption of the dimerized and polymerized TG (3, 4) as well as an effective detoxifying capability by the liver microsomal enzymes, including cytochrome P450 monoxygenase and phase II conjugation enzymes (5). The enlarged liver was thus speculated to be related to the increased microsomal protein since routine histo pathological examination did not reveal significant alterations (Cheung and Huang, unpublished data).