AIM: To investigate oxidative stress and lipid peroxi-dation in hepatic steatosis and the underlying implica-tions in pathological mechanisms of non-alcoholic fatty liver disease (NAFLD).METHODS: F2-isoprostanes (iPF2α-Ⅲ) in blood and liver samples from steatotic (n = 9) and control (n = 7)rats were measured as in vivo marker of lipid peroxida-tion by a mass spectrometric approach. The lipid pro-file and endogenous antioxidant status (SOD and CAT)in the rats were also analyzed.RESULTS: Significantly higher levels of iPF2α-Ⅲ (mean3.47 vs 2.40 pmol/mg tissue, P = 0.004) and lower activities of SOD (mean 1.26 U vs 1.40 U, P < 0.001) and CAT (mean 1026.36 U/mg vs 1149.68 U/mg pro-tein, without significance) were observed in the livers of steatotic rats. Plasma total iPF2α-Ⅲ was significantly correlated with the abnormalities of blood lipids as well as alanine aminotransferase (ALT) levels in the rats with simple steatosis, whereas no similar tendencies were observed in the control rats.CONCLUSION: Enhancement of hepatic oxidative imbalance occurring at the steatotic stage of NAFLD suggests a possibility that manifestation of the local oxidative damage precedes that of systemic oxidativeimbalance. Predominant metabolic features of the in-creased lipid peroxidation further suggest a close asso-ciation of the oxidative imbalance and the dyslipidemia with functional deterioration of the steatotic liver. The findings need to be further evaluated, especially in hu-man studies.