Moringa oleifera leaves have therapeutic functions such as antioxidant, anti-bacterial, anti-viral, 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 diet-induced 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.