Introduction: One of the widely used gastro protective agents are H2 receptor antagonists (H2RAs). But these drugs may induce several adverse effects. Recent studies have shown that mesenchymal stem cells (MSCs) play an important role in the healing of gut injuries.  Aim of the work: To evaluate the role of bone marrow- mesenchymal stem cells (BM- MSCs) in the treatment of gastric ulcer, and to compare their efficacy with H2RAs therapy.  Methods: 10 out of the 50 adult albino rats used in this study served as donors for stem cells and the other 40 rats were divided into four groups: Group I (control group). Group II (Gastric ulcer group < /em>), rats received 200mg /kg ibuprofen suspended in CMC-Na 1% given orally by gastric tube. Group III (Nizatidine treated group), rats with gastric ulcer were treated with 31.25 mg/kg nizatidine, given orally by gastric tube. Group IV (BM-MSCs treated group < /em>), rats with gastric ulcer were injected with BMMSCs in the rat tail vein.  Results: MSCs-treated group revealed improvement of histological structure and restoration of the normal architecture of the gastric mucosa. Nizatidine-treated group demonstrated nearly similar results to that of MSCs treated group. A significant decrease of tumor necrosis factor α (TNF-α) expression was observed in MSCs-treated group as well as nizatidine-treated group when compared to ulcer group (P<0.01).  Conclusion: MSCs could be a safer alternative therapy than H2RAs, with the benefit of avoiding the side effects of these drugs.