BACKGROUND: Hepatic steatosis due to estrogen therapy increases the activity of inflammatory markers, particularly the activity of TNFa which in turn induces more lipogenesis.Omega-3 fatty acids are among the negative regulators of hepatic lipogenesis.OBJECTIVES: In this research, the preventive effect of omega-3 fatty acids on estrogen-induced steatosis in rats was evaluated.METHODS: 2 mg/kg. BW/SC of 17a-ethiny-lestrasdiol were injected into 25 female wistar rats in 5 equal groups (excluding the control group) over 10 consecutive days.Simultaneously, 3 of estradiol-treated groups were orally given 250, 500, and 1000 mg/kg. BW omega-3 fatty acids, respectively.At the end of the experiment, plasma ALT, AST, and TNFa level were determined. Histopathological changes in the liver were also identified by the evaluation of samples stained with H& E and Oil Red O.RESULTS: The histological findings revealed hepatic microvesicular steatosis and fat deposit in ethinylestradiol and, to a lesser extent, in the 250 mg/kg BW omega-3 fatty acids groups. The plasma levels of AST, ALT, and TNFa significantly increased in the ethinylestradiol group compared to the control (p<0.05) and 1000 mg/kg. B.W omega- 3 group. Omega-3 fatty acids reduced these parameters in comparison to the estradiol group (p<0.05).CONCLUSIONS: It was concluded that 1000mg/kg.BW of omega-3 protects the liver against steatotic injuries.