Gastrointestinal disorders is a serious problem of the human population. Stress is known to contribute to the development and progression of gastrointestinal disorders. The hypothalamic- pituitary-adrenal (HPA) axis activation belongs to the main characteristics of the stress. For a long time it has been generally accepted that glucocorticoids released during stress, are harmful ulcerogenic hormones, a notion that is difficult to reconcile with the adaptive role of HPA axis. We designed some experimental studies to clarify the validity of this dogma. For this aim, we examined the effect of glucocorticoid deficiency (created by different approaches and followed by corticosterone replacement) or the glucocorticoid receptor antagonist RU-38486 on stress-induced gastric erosion and parameters of gastric function in rats. The data obtained show that the reduction in the stress-induced corticosterone release, or its actions, aggravates stress-caused gastric erosion. It is suggested that an acute increase in corticosterone during stress protects the stomach against stress-induced injury. Accordingly our results various ulcerogenic stimuli, similar to stress, induce an increase in glucocorticoid production that helps the gastric mucosa to resist against a harmful action of ulcerogenic stimuli. The contribution of glucocorticoids to gastroprotection is tightly related with their contribution to general body homeostasis. Furthermore, they exert gastroprotective actions in co-operation with prostaglandins, nitric oxide and capsaicin- sensitive sensory neurons. The results suggest that glucocorticoids released during acute activation of the HPA axis are naturally occurring gastroprotective factors. Supported by FNM RAS-2009, RFBR-07–04–00622, OBN RAS-2009, Sci School 1432.2008.4.