The present study was performed to evaluate the anti-ulcerogenic activity of Acacia Senegal (Gum Arabic) against ethanol-induced gastric mucosal injury in rats. Thirty-six adult male albino rats were divided into four groups: group (1) served as a control, group (2) consists of rats received 15% of gum in drinking water for two weeks, group (3) contains ulcerated animals administered 5 ml of ethanol/ kg b.wt. by gavage, group (4) consists of rats received 15% of gum in drinking water for two weeks before ethanol administration. Superoxide dismutase (SOD) glutathione peroxidase (GPX), malondialdehyde (MDA), prostaglandin (PGE2), tumor necrosis factor (TNF-α), interleukin (IL-B1), ALT, AST, alkaline phosphatase, total protein and albumin, were assayed, in addition to histological study. The results revealed that ethanol decreased SOD, GPx and PGE2 in tissue and serum total protein and albumin, while increased MDA in tissue, serum TNF-α, IL-B1, PGE2, ALT, AST, ALP. Histological findings showed less edema and leucocytes infiltration compared to ulcer group. Furthermore, gum administration elevated PGE2, SOD, and GPx and significantly reduced MDA, TNF-α and IL-B2. In conclusion Gum Arabic can enhance gastric protection and sustain the integrity of the gastric mucosa. Novelty: • The selected dose of Gum Arabic has the ability to decrease the pro-inflammatory cytokines in plasma and gastric tissue, thus enhances gastric protection and keeps the integrity of the gastric mucosa. • Gum Arabic can compensate the loss of antioxidants.