Selye recognized the importance of activation of hypothalamic-pituitary-adrenal axis during stress and the connection between central nervous system and neuroendocrine regulation. This concept basically contributed to initiation of the studies, which revealed the importance of brain gut axis in regulation of gastric mucosal integrity. Several neuropeptides, such as thyreotrop releasing hormones, adrenomedullin, peptide YY, amylin, opioid peptides, nociceptin, nocisatin, substance P, ghrelin, leptin, orexin-A, angiotensin II were shown to induce gastroprotective effect injected centrally. Though the involvement of dorsal vagal complex and vagal nerves in conveying the central action to the periphery has been well documented, additional mechanisms have also been raised. The interaction between neuropeptides further component that may modify the gastric mucosal resistance to noxious stimulus.