We previously reported that dexamethasone pretreatment abolishes the refeeding-induced neuronal nitric oxide synthase (nNOS) expression in the rat paraventricular nucleus (PVN). It was reported that nNOS upstream carries cAMP response element (CRE) and nNOS expression is mediated by a CRE-binding protein (CREB)-dependent mechanism. In this study, CREB phosphorylation was co-localized in the nNOS neurons of the rat PVN regardless of feeding conditions. The relative amount of phosphorylated CREB in the hypothalamic tissue lysates increased by 1 h of refeeding following 48 h of food deprivation, and interestingly, this increase was blocked by dexamethasone administration before the food onset. These results suggest that glucocorticoids exert an inhibitory role in CREB phosphorylation directed by nutritional stimuli in the rat hypothalamus, and this inhibition may be related to nNOS gene expression in this brain region.