The results overviewed in the present article suggest that glucocorticoids released during acute activation of hypothalamic-pituitary-adrenocortical (HPA) axis are important gastroprotective factors, allowing us to re-evaluate the traditional point of view about their ulcerogenic role. It has been shown that various ulcerogenic stimuli induce an increase in glucocorticoid production that in turn helps the gastric mucosa to resist against a harmful action of ulcerogenic stimuli. Glucocorticoids released in response to mild stress contribute to adaptive gastric cytoprotection. The gastroprotective action of glucocorticoids is accounted for by maintaining the local defensive factors and inhibiting the pathogenic elements. Maintenance of glucose and temperature homeostasis as well as systemic blood pressure by glucocorticoid hormones could be a fundamental of their beneficial action on various gastric targets. Thus, glucocorticoids released during activation of HPA axis may contribute to the gastric mucosal homeostasis through their contribution to general body homeostasis.