Moreover, the offspring of mothers displaying high levels of maternal care, increased their exploratory Rapamycin behaviour and spatial memory and reduced their anxiety-like behaviour. In our previous studies conducted in rats, we have shown that offspring nursed by mothers with a mild hypercorticosteronemia develop the ability to cope better with different situations during life. In this animal model, the drinking water of mother rats during lactation was supplemented with corticosterone. Maternal corticosterone is in equilibrium between blood and milk in rodents, and the hormone is easily absorbed by the gastrointestinal tract of the pups, as the glucocorticoid permeability of the gut is very high in early postnatal life up to 17–18 days of age. With this approach a moderate increase in corticosterone may be achieved in the mother as well as in the pups without disturbing them. The progeny of these mothers, once adults, showed improved learning capabilities, reduced fearfulness in anxiogenic situations and, more interestingly, resistance to ischemic neuronal damage. The protective long-life effect of hormonal manipulation in CORTnursed rats is strictly linked to a persistent hyporeactivity of the HPA axis due to an increased number of glucocorticoid receptors in the hippocampus, a recognized target of glucocorticoid negative feedback action. To our knowledge, there have been no studies considering the effect of such a positive postnatal manipulation on the homeostasis of the gastrointestinal tract. Therefore, the aim of the present study was to investigate the susceptibility to inflammatory colitis induced by intracolonic infusion of TNBS in adult CORT-nursed offspring. The data presented in this work show the long lasting effect of mildly increased maternal corticosterone during lactation on TNBS colitis in three-month old male rats, and take into account the variations in some indices of the pathology and the involvement of the main peripheral endogenous systems: mast cells, glucocorticoids and their receptors, corticotrophin releasing factor and its receptor, CRH-1R, known to be involved in the onset and progression of colitis. This is the first study indicating the beneficial effect of positive postnatal manipulation on the homeostasis of the gastrointestinal tract in the presence of an inflammatory disease. In fact, adult male rat progeny of mothers whose drinking water was supplemented during lactation with moderate doses of corticosterone had a reduced vulnerability to TNBS-induced experimental colitis. Such a protective effect is revealed by improvements in several indices of the pathology, and well correlated with a decrease in colonic mast cell degranulation. Conversely, colitic CORT-nursed rats, in comparison with colitic controls, did not show any variations in histological scores or in the typical shortening of intestinal length. It is important to note, however, corresponding to the maximum level of inflammation, when the healing process, responsible for recovery from the ulcers, oedema and restoration of a normal intestinal length, was probably not yet manifested. Thus, we cannot exclude in a late phase recovery from these clinical signs could also be accelerated.