The recent dramatic increase in fructose consumption is tightly correlated with an equally dramatic surge in incidence of type II diabetes and obesity in children, but little is known about dietary fructose metabolism and absorption in neonates. The expression of the rat intestinal fructose transporter GLUT5 can be specifically induced by its substrate fructose but only after weaning begins at 14 d of age. In suckling rats < 14 d old, dietary fructose cannot enhance GLUT5 expression. The aim of this study was identify the mechanisms allowing fructose to stimulate GLUT5 during weaning. After intestines were perfused with fructose or glucose (control), we showed using microarray hybridization that of 5K genes analyzed in 10 d old pups, only 13 were fructose-responsive. Previous work found 50 fructose-responsive genes in 20 d old pups. To identify fructose-responsive genes whose expression also changed with age, intestines of 10 and 20 d old littermate pups perfused with fructose were compared by microarray. Intestines of 10 and 20 d olds perfused with glucose were used to segregate age- but not fructose-responsive genes. About 28 genes were up- and 22 downregulated in 20 relative to 10 d old pups, under conditions of fructose perfusion, and many were found, by cluster analysis, to be regulated by corticosterone. When dexamethasone (dex) was injected into suckling pups prior to fructose perfusion, GLUT5 but not SGLT1 nor GLUT2 expression, and fructose but not glucose uptake increased dramatically. Thus, dex which allows dietary fructose to precociously stimulate intestinal fructose absorption can mimic the effect of age and modify developmental timing mechanisms regulating GLUT5.