Hypothalamic-Pituitary-Adrenal (HPA) axis hyperactivity occurs in Type 2 Diabetes, and stress is assumed to play a causal role. However, intermittent restraint stress, a model mimicking some mild stressors, delays development of hyperglycemia in ZDF rats. We examine whether such stress delays hyperglycemia independent of stress-induced reductions in hyperphagia, and is due to adaptations in gene expression of HPA-related peptides and receptors that ameliorate corticosteronemia and thus hyperglycemia. ZDF rats were intermittently restraint stressed (1hr/day, 5days/wk) for 13wks and compared to obese control, pair fed, and lean ZDF rats. After 13wks, basal hormones were repeatedly measured over 24hrs, and HPA-related gene expression assessed by in situ hybridization. Although restraint initially induced hyperglycemia, this response habituated over time and intermittent restraint delayed hyperglycemia. This delay was partly related to 5–15% decreased hyperphagia, which was not accompanied by decreased arcuate nucleus NPY or increased POMC mRNA expression, although expression was altered by obesity. Obese rats demonstrated basal hypercorticosteronemia and greater corticosterone responses to food/water removal. Basal hypercorticosteronemia was further exacerbated after 13wks of pair feeding during the nadir. Importantly, intermittent restraint further delayed hyperglycemia independent of food intake, since glycemia was 30–40% lower than after 13wks of pair feeding. This may be mediated by increased hippocampal MR mRNA, reduced anterior pituitary POMC mRNA levels, and lower adrenal sensitivity to ACTH, thus preventing basal and stress-induced hypercorticosteronemia. In contrast, 24hr catecholamines were unaltered. Thus, rather than playing a causal role, intermittent stress delayed deteriorations in glycemia and ameliorated HPA hyperactivity in the ZDF rat.