Objective To elucidate the molecular mechanisms of the potent anti-obesity effect of Moringa oleifera Lam. (M. oleifera) ethanolic extract and to clarify the link between these mechanisms and the associated metabolic and vascular risks in the experimental model of visceral obesity. Methods M. oleifera ethanolic extract was orally administered at 600 mg/kg body weight in obese female rats daily for 12 weeks. At the end of treatment, body weight was determined, and the atherogenic index, coronary artery index, glucose level, insulin resistance status, liver and kidney functions were assessed. Also, the mRNA of leptin, adiponectin and resistin in visceral adipose tissue was determined by quantitative real time-PCR. Results The results showed that M. oleifera extract down-regulated mRNA expression of leptin and resistin, while it up-regulated adiponectin gene expression in obese rats relative to untreated obese control counterparts. This amelioration of genes expression was paralleled by a reduction in body weight and improvement of the atherogenic index and coronary artery index, as well as glucose level and insulin resistance value without adverse effects on liver or kidney functions, versus the untreated obese control ones. Conclusions It is reasonable to assume that the anti-obesity, anti-atherogenic and anti-diabetic properties of M. oleifera are mechanistically achieved via working directly on the adipokines of the visceral adipose tissue. Therefore, M. oleifera may be a good therapeutic candidate for the symptoms of metabolic syndrome.