Background: Peptic ulcer represents a serious medical problem due to theirfrequency among different socioeconomic classes. Although treatment with protonpump inhibitors (PPIs) and antibiotics has revolutionized the treatment of pepticulcers, in some patients the ulcer is either refractory to conventional therapy, orrecurs following successful initial treatment, leading to hemorrhagiccomplications. Refractory peptic ulcer remains a great challenge togastroenterologists. Therefore, new alternative therapies for injured gastric mucosaare needed . The key factor in modulating microcirculation is nitric oxide (NO),Moreover, it plays a significant role in gastric ulcer healing. Also Bone marrowmesenchymal stem cells(BMMSCs) contribute to the formation of gastrointestinaltissues and has an important role in the healing of gut inuries. From this aspect weevaluated the effect of mesenchymal stem cells (MSCs) and NO on induced gastriculcer rat model.Methods: Seventy two rats which were divided into: control group (8rats),and 16 rats for each of the following groups: Gastric ulcer group, Gastriculcer group received the MSCs, Gastric ulcer group received NO inducer, Gastriculcer group received MSCs plus NO inducer after 24 hours and 7 days.Histopathological examination of gastric tissues, gene expression of HGF, eNOS,caspase-3, Bax and bcl2 in gastric tissue, and estimation of serum VEGF, PGE2and TNF-α by ELISA were done.Results: Histopathological examination of gastric tissue from gastric ulcergroup animals revealed focal necrosis and ulceration. Administration of MSCs, orNO, or MSCs with NO improved the histopathological picture with almost healedulcer. Gene expression demonstrated that HGF,eNOS and bcl2 were upregulatedwhile Bax and caspase-3 genes were downregulated in all treated groups with more significant effect in the group treated with MSCs plus NO. Level of VEGF wasincreased while of PGE2 and TNF-α were decreased in all treated groups, but withmore significant effect in the group treated with MSCs plus NO.Conclusion: Administration of BM-MSCs alone, NO alone, or BM-MSCsplus NO exerts a therapeutic effect on the gastric mucosal lesion in Gastric ulcer.This effect may be through the anti-inflammatory, angiogenic and antiapoptoticactions of both MSCs and NO.