1 Departmentof Medical Physiology, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo, Egypt 2 Department of Biochemistry, Kasr Al Aini Faculty of Medicine, Cairo University, Cairo, Egypt Corresponding Author Hader Ibrahim Sakr, MD Department of Medical Physiology, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo Egypt Email: hadersakr209@yahoo.com, hadersakr@kasralainy.edu.eg Mobile phone: +201111616364 Postal code:11451 ABSTRACT A gastric ulcer is a break in the normal gastric mucosa integrity that extends through the muscularis mucosa into the sub-mucosa or deeper. This work aimed to study the effect of chronic administration of vinegar on gastric acid secretion, and if this action has any effect on stress-induced ulcer in male albino rats. Study groups included 24 rats divided into 2 main groups (12 rats/group): pyloric ligation group (A) and water immersion-induced gastric ulceration group (as a form of stress) (B). We evaluated; free and total HCL secretion in group A, ulcer score, ulcer index, percentage ulcer protection, , eNOS enzyme activity, COX-2 enzyme activity, glutathione reductase gene expression, CCK gene expression and proton pump (H + /K +