Intermittent restraint stress delays hyperglycemia in ZDF rats better than pair feeding. We hypothesized intermittent stress would preserve -cell mass through distinct mechanisms from food restriction. We studied temporal effects of intermittent stress on -cell compensation during pre-, early-, and late-diabetes. 6wk old obese male ZDF rats were restraint stressed 1hr/day, 5days/wk for 0, 3, 6, or 13wks and compared to age-matched obese ZDF, obese ZDF rats that had been food restricted for 13wks, and 19wk old lean ZDF rats. 13wks of stress and food restriction lowered cumulative food intake 10-15%. Obese islets were fibrotic and disorganized and not improved by stress or food restriction. Obese pancreata had islet hyperplasia and showed evidence of neogenesis but by 19wks old -cell mass was not increased, and islets had fewer -cells that were hypertrophic. Both stress and food restriction partially preserved -cell mass at 19wks old via islet hypertrophy, while stress additionally lowered -cell mass. Concomitant with maintenance of insulin responses to glucose, stress delayed the 6-fold decline in -cell proliferation and reduced -cell hypertrophy, translating into 30% more -cells per islet after 13wks. In contrast, food restriction did not improve insulin responses or -cell hyperplasia, exacerbated -cell hypertrophy, and resulted in fewer -cells and greater -cell mass than with stress. Thus, preservation of -cell mass with adaptation to intermittent stress is related to -cell hyperplasia, maintenance of insulin responses to glucose, and reductions in -cell mass that do not occur with food restriction.