Non-alcoholic fatty liver disease (NAFLD) is a serious global health problem that is strongly linked to insulin resistance, obesity, and oxidative stress. The goal of current work was to inspect the hepatopro-tective and hypolipidemic effects of Phyllanthus niruri ethanolic extract (PNEE) on high fat hyperlipidemic diet –induced rat's fatty liver. A unique high-fat diet (HFD) composed of coconut oil (7.3%), beef tallow (7.3%), safflower oil (0.4%) and cholesterol (1.5%) were used in the present study for induction of NAFLD or hyperlipidemia in male Albino rats. Forty-eight clinically healthy male Albino rats were equally divided into four groups: the first served as control. The second group, rats administered ethanol extract of Phyl-lanthus niruri (PN) (250 mg/kg b.wt.); while the third group was rats fed diet supplemented high fat con-centrated (HFCD); and the fourth was rats received combination of HFCD and PN (HFCD+PN). All treat-ments were given daily by oral route for 105days. All treatments were given daily by oral route for 105 days. Treatment of hyperlipidemic rats by PNEE resulted in reduction of serum liver enzymes, and im-provement in proteins and lipids profile, as well as pancreatic function tests, in comparison with hyper-lipidemic rats (gp.3) which showed severe biochemical alterations. This was confirmed by histopatholog-ical findings in the liver. It could be concluded that PNEE treatment has a strong hepatoprotective impact against fatty alterations in animal models, suggesting that PNEE could be used as a promising agent to prevent fatty liver disease.