Background: Non alcoholic fatty liver disease (NAFLD) is an increasing health problem which affects about 1/3 of the population worldwide, it is strongly associated with metabolic syndrome with oxidative stress and insulin resistance are the mechanisms mostly involved in its pathogenesis. Dipeptidyl peptidase-4 inhibitors are antidiabetic agents expected to have beneficial effects beyond their glycemic control. Aim of the Study:The present work was designed to study the beneficial effects of sitagliptin (a DPP-4I) on a dietary model of NAFLD.Material and Methods: 30 male albino rats were allocated in 3 groups. The effects of sitagliptin, was assessed in groups III. Body weight and blood pressure were recorded and blood samples were tested for total cholesterol, triglycerides and liver transaminases, glucose and insulin levels. Livers for GSH, MDA, TGF-B and DPP-4 activity and for histopatholgical examination. Aortae were removed for in vitro vascular reactivity studies.Results: Induction of NAFLD model by HFD for 20 weeks resulted in significant increase in body weight, blood pressure, liver index and epididymal weight. Significant reduction of these parameters was observed with 4 week treatment with sitagliptin. There was significant increase in all biochemical parametres in HFD fed rats compared to that of normal with significant improvement in sitagliptin treated group. HFD model groups showed notable steatosis, lobular inflammation and fibrosis which was improved with sitagliptin use. Also NAFLD rats developed endothelial dysfunction which was significantly ameliorated in sitagliptin treated group. Conclusion:The results of the present work showed that the DPP4Is have the potential to favorably influence the course of NAFLD process and its complications. DPP4I (sitagliptin) has many beneficial effects including scavenging of free radicals, and enhancing the activity of antioxidant effects. Large clinical trials are needed to determine the effectiveness of DPP-4 inhibitors for the prevention and treatment of NAFLD