Background: Gastroesophageal reflux disease (GERD) is one of the most common problems encountered in clinical practice today. The pathophysiology of GERD is complex, involving diverse factors. Aim of the work: was to assess the role of visceral fat and IL-6, adiponectin and leptin levels on reflux esophagitis in obese patients. Patients and Methods: This prospective observational case-control study included a total of 90 participants; 60 patients with reflux esophagitis and 30 age and sex-matched healthy controls. Evaluation of the Role of Visceral Fat, IL-6, Adiponectin and Leptin Levels on Reflux Esophagitis in Obese Patients was done. Results: An overall 90 patients were enrolled in this study, 50 males and 40 females, were assorted into three groups, obese and had GERD group, non-obese and had GERD, included 30 patients (33.3%),17 males (56.7%) and 13 females (43.3%), and control group, included 30 patients (33.3%),18 males (60%) and 12 females (40%). The mean levels of body mass index, weight circumference, fasting-plasma glaucous, two hours post-prandial plasma glucose, Creatinine, liver enzymes, and lipid parameters were elevated in obese group when compared with non-obese and control groups. Consequently, the mean levels of leptin and interleukin-6 were high in obese group in comparison with other groups. Interestingly, the mean level of adiponectin was high in non-obese group in comparison with obese and control groups. Conclusion: Inflammatory cytokines, adipokines, and visceral fat referring abdominal obesity had an association with reflux esophagitis.