INTRODUCTION The increasing in the epidemic of obesity has been associated with doubling in the incidence of diabetes mellitus over the last 30 years especially in those with body mass index (BMI) ≥30 kg/m 2 , underscoring the close linking between obesity and metabolic syndrome. 1 Visceral adipose tissue secretes a variety of bioactive substances that might ABSTRACT Background: Insulin resistance impairs nitric oxide (NO) bioavailability; obesity promotes a state of metabolic syndrome and damages the vascular endothelium by altering lipid profile. Phosphodiesterase-5 (PDE-5) inhibitors restore NO signaling may improve metabolic parameters through a number of mechanisms. We hypothesized that daily administration of the PDE-5 inhibitor; sildenafil will improve fasting plasma glucose (FPG), triglyceride (TG) levels and body weight, in obese diabetic patients. Methods: Totally, 25 obese diabetic male patients with metabolic syndrome treated with sildenafil 25 mg daily for 3 months. Body weight, FPG levels, and lipid profile were determined monthly. Results: Treatment with sildenafil caused a reduction in fasting glucose levels, fasting TGs, cholesterol, low-density lipoprotein (LDL), very-LDL and increased high-density lipoprotein; body weight was significantly reduced. Conclusion: We have provided the first evidence that sildenafil therapy improve glycemic control, lipid profile and body mass index in diabetic patients with metabolic syndrome.