Previous study pointed to an important role of adrenals and glucocorticoids in the trophic status of the adult small intestine mucosa, with possible implications during stress events. Small intestine morphological and biochemical consequences of 10-day bilateral adrenalectomy and also sham-related laparotomy were determined in 23-month-old Sprague-Dawley rats. As described in young rats, adrenalectomy in old rats leads to partial atrophy and disorganization of the proximal small intestine epithelium, with an increase in the number of Paneth cells and reduced crypt cell proliferation. We also observed a decrease of goblet cell number and a reduction of all enzyme activities including disaccharidases, in contrast with the specific induced response shown in young rats. A number of marked biochemical effects have also been noted in aged rats subjected to solely laparotomy, suggesting age-related adaptation impairments. In conclusion, adrenalectomy modified the differentiation processes of the small intestinal mucosa in both young and aged rats, and some parameters underlined that the lack of corticoid-mediated adaptive process are exacerbated by cumulative surgical stress (event) and aging.