Background: Pomegranate peel extract (PPE) is known to possess bioactive compounds such as phenolics and flavonoids, considered among the more potent antioxidants and anti-inflammatory sources.Aims: This study was designed to evaluate PPE activity's protective effect as a natural therapeutic against peptic ulcers induced by Brexin.Methods: 40 rats were divided into four groups: Control group: ten rats received normal saline treatment; Brexit group: ten rats received a single oral dose of Brexit

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... to induce the stomach ulcer; Antodine group: ten rats received Antodine (50 mg/kg) as a commercial drug for the peptic ulcer treatment once for two weeks following a peptic ulcer; Pomegranate group: ten rats of the group received PPE (43 mg/kg) treatments. Histological, histochemical, immunohistochemical techniques were used to detect histopathological damages in stomach rats in all groups.Results: The histopathological results showed that PPE treatments following Brexin-induced peptic ulcer ameliorated histological degenerative changes in the gastric glandular. Chief and surface mucous cells that are lining gastric mucosa were regained when compared with the other groups. The histochemical results showed that PPE treatment following ulcer provided an improvement in the secretion and distribution of the polysaccharides in the epithelial cells when compared with the other groups. Also, immunohistochemical results indicated a significant decrease in immunoreactivity of cytokeratin-20, cyclooxygenase-2, and proliferating cell nuclear antigen (PCNA) in epithelial cells of rats in ulcer-model when compared with the other groups.Conclusion: PPE revealed its antiulcer activity and is recommended as a natural remedy against gastric mucosal injury induced by Brexin.