Moringa Oleifera leaves have therapeutic functions such as antioxidant, anti-bacterial, antiviral, anti-cancer, anti-inflammatory, anti-allergic and anti-diabetic. The purpose of this study was to evaluate the protective effect of Moringa Oleifera on obesity induced oxidative stress and biochemical abnormalities in male rats. Forty-eight male albino rats were divided into three equal groups. Group I (control normal): rats fed normal diet. Group II (Obesity): rats received high fat diet (HFD).Group III (Obesity+ Moringa oleifera): rats received Moringa Oleifera (600 mg/kg.b.wt.) orally for two months after induction of obesity. The obtained results showed significant increase in levels of serum insulin, lipids profile (total cholesterol and triacylglycerols), liver L-MDA in addition to up regulation of Leptin and Nuclear factor kappa B (NF-κB) gene expression level in obese rats. However, liver catalase activity and GSH concentration were markedly decreased. Moringa Oleifera treatment to high fat dietinduced obesity in rats caused significant improvement of all previous parameters towards its normal ranges. These results suggested that, Moringa Oleifera treatment exerts a protective effect on obesity by reduction of oxidative stress markers, inflammation and hyperlipidemia in rats through free radical scavenging and anti-inflammatory activities as well as regenerating endogenous antioxidant defense system mechanisms.