Nonalcoholic fatty liver disease (NAFLD) is sickness with different causes and it is the most hepatic illness. The objective of this work is to investigate the bimolecular changes in a model of high fat diet induced- NAFLD in rats. Also, the hypolipidemic, antioxidant and anti-inflammatory effects of omega-3 were clarify via evaluation of some biochemical and molecular parameters in the liver tissue of rats.Twenty one adult white albino rats were divided into three groups. Group I (Normal control): received no drugs and fed balanced diet, Group II (NAFLD- induced group): rats fed high fat diet for 8 weeks followed by normal basal ration for additional 8 weeks. Group III (NAFLD + omega-3): rats administrated omega-3 (300 mg/kg b.wt/day), orally for 8 weeks post-induction of NAFLD. The obtained results showed a significant increase in serum Total cholesterol and Triacylglycerols (TAG) concentrations, L-MDA and TAC in liver tissue with significant up-regulation in CPT-1α, FAS, SREBP-1c, PPAR-α, Nrf2 and TAK1gene expression in NAFLD-induced rats. Treatment with Omega-3 to NAFLD induced rats potentially improved molecular hepatic cell function and oxidative alterations related to NAFLD near its normal ranges. Meanwhile, histo-pathological findings supported that Omeg-3 markedly attenuates harmful effects of NAFLD and protected liver cell. On conclusion, Omega-3 plays an important role as potent anti-oxidant, anti-obesity, anti-inflammatory via inhibition of hepatic steatosis and oxidative stress singling.