The Egyptian Journal of Histology 2011, 34:546–553 50 (1287 -2011) Background Peptic ulcer is a serious disease with a high incidence of occurrence in our community. Gum arabic (GA) is an edible, dried, gummy exudate from the stems and branches of Acacia senegal. It has been claimed to act as an antioxidant. Aim of the study The aim of this study was to evaluate the protective effect of GA on stress-induced peptic ulcer in rats. Material and methods In this study, 30 adult male rats were divided equally into three groups: the control group (group I), the stress ulcer group (group II), and the GA group (group III); the GA group received GA 7.5 g/kg/day through an orogastric tube for 10 days. After 10 days, the rats were fasted for 24 h. Cold immobilization stress was induced in groups II and III. The animals of all groups were then anesthetized with diethyl ether, and their stomachs were isolated immediately, opened from the greater curvature, and washed with saline. Ulcer severity, ulcer score, and ulcer index were determined. Stomach specimens were fixed in 10% neutral-buffered formalin for histological, hematoxylin and eosin, histochemical, Periodic Acid Schiff’s (PAS), and Masson’s trichrome stainings and for immunohistochemical detection of proliferating cell nuclear antigen (PCNA). Results Pretreatment with GA significantly decreased the gastric lesions. Both ulcer severity and score were significantly decreased (32.8% and 39.58%, respectively) compared with the stress-untreated group. Ulcer index was significantly decreased (49%) compared with the stress group (P < 0.05). The stress group showed atrophic gastric mucosa with loss of glandular tissue (hematoxylin and eosin), positive PAS reaction in the mucus neck cells, many collagen fibers between the atrophic glands, and moderate PCNA reaction in the glandular cells. In the GA group, there was nearly normal gastric mucosa with a small area of atrophied surface epithelium, PAS-positive reaction in surface and neck mucus cells, some collagen fibers between the near normal gastric glands, and mild PCNA reaction in the gland cells. Conclusion It can be concluded that GA exerts a protective effect against stress-induced gastric mucosal lesions in rats.