The hypothalamus-pituitary-adrenal (HPA)-axis is hyperactive under conditions of leptin and insulin resistance as well as after angiotensin II (ANG) administration. We hypothesized that a hyperreactivity of the HPA-axis to ANG contributes to an impaired glucose utilization in obesity, since leptin resistance and a overactive renin-angiotensin-aldosterone system are features of obesity. Zucker rats were treated with ANG via subcutaneous minipumps (0, 0.9, 9.0µg/h; 4 weeks). Pituitary-adrenal-axis reactivity and glucose homeostasis were characterized after corticotrophin-releasing-hormone (CRH) treatment and during an oral glucose-tolerance-test (OGTT). The elevated plasma profile of corticosterone after CRH-stimulation in saline-treated obese (OZR) compared to lean Zucker rats (LZR) confirmed that the sensitization of the pituitary-adrenal-axis depended on leptin resistance. Irrespective of the rat strain, circulating ANG-levels and blood pressure were selectively increased after administration of 9µg/h ANG (high-ANG). Only high-ANG induced an elevation of the corticosterone and glucose response after CRH-stimulation in OZR, but did not affect the ACTH-secretion. During OGTT, corticosterone and consequently glucose increased in OZR after high-ANG, whereas the insulin secretion was decreased. In the adrenal glands of OZR, AT_1A-receptor mRNA levels increased after high-ANG. We conclude that the impairment of glucose utilization after ANG-stimulation is potentiated in leptin resistant rats as a result of a hyperreactive pituitary-adrenal-axis, thereby confirming the functional importance of a dysregulation within the HPA-axis in metabolic syndrome or obesity. The ACTH-independent stimulation of corticosterone release and the selective increase of AT_1A-receptor mRNA in the adrenals of OZR indicated a sensitization of adrenals towards ANG causing a stimulation of the pituitary-adrenal-axis.