Non Alcoholic Fatty Liver Disease (NAFLD) is now the commonest liver disease worldwide and can evolve into cirrhosis in a subgroup of patients. Sildenafil citrate is a specific phosphodiesterase-5 (PDE-5) inhibitor, which has been approved for treatment of erectile dysfunction in men. To examine the effect of sildenafil citrate on NAFLD in animal model and male patients with erectile dysfunction. Sixty male mice were divided into 4 groups: The 1-received a standard diet; 2-fed with a High-fat Diet (HFD); 3-HFD + sildenafil citrate; 4-standard diet + sildenafil citrate. The experiments were conducted for 16 weeks, after that, the mice in the treatment groups received 1.4 mg kg–1 sildenafil citrate base dissolved in distilled water daily for 8 weeks, through orogastric feeding tube. A case-control study enrolled 60 males with erectile dysfunction, who were divided into 30 patients with NAFLD and 30 patients without NAFLD (control group). They received sildenafil citrate 50 mg daily for 8 weeks. It was found that sildenafil administration improved liver enzymes, insulin resistance and lipids level compared to control group in animal model. There were insignificant changes as regard lipid profile, fasting serum insulin and liver enzymes (alkaline phosphatase, alanine 2-oxoglutarate aminotransferase) after sildenafil treatment for 8 weeks in NAFLD group in human study. There was significant decrease in aspartate 2-oxoglutarate aminotransferase (AST) level after sildenafil treatment in NAFLD. There were significant negative correlations between International Index of Erectile Function (IIEF) score and Body Mass Index (BMI), cholesterol and triglycerides levels. Sildenafil is well-tolerated and safe in NAFLD patients. However, it is less effective in NAFLD patients than in individuals without comorbidities. Further investigation is needed to test the effect of long-term sildenafil administration on insulin resistance and lipid profile.