Aging is associated with deregulation of glucose homeostasis and with morphological and functional alterations in the carotid body (CB) (1). The CB is an oxygen sensor being also involved in energy and glucose homeostasis. Resection of carotid sinus nerve (CSN), the CB sensitive nerve, has shown to prevent and reverse insulin resistance and glucose intolerance induced by hypercaloric diets (2-4). Herein, we evaluated the effect of CSN resection on metabolic dysfunction induced by ageing and by long-term hypercaloric diet consumption in rats. Also, since animal models of dysmetabolism and metabolic syndrome patients exhibit increased CB chemosensitivity (2,5), we tested CB function in hypercaloric diet-old animals. Male Wistar rats (8-10 weeks) were used: a control (CTL, n=12) group that fed a chow diet and a high-fat high-sucrose (HFHSu, n=15) group that fed a 60% lipid-rich-35% sucrose diet during 44 weeks. Groups were randomly divided, anesthetized (medetomidine 0.5 mg/kg; ketamine 75 mg/kg) and submitted to CSN resection or to a sham surgery, with 9 weeks follow-up. Insulin sensitivity and glucose tolerance were evaluated as well as fasting glycemia, insulinemia, C-peptide and ventilatory responses to hypoxia. At a terminal experiment, fat depots were analyzed. CB dysfunction was evaluated through the morphometric analysis of CBsfor tyrosine hydroxylase (TH), GFAP and nestin-positive cells. One- and two-way Anova tests were used. Ageing and long-term HFHSu consumption decreased insulin sensitivity by 59.11 (p<0.0001) and 58.11% (p<0.0001), respectively (KITT CTL= 4.50±0.36%glucose/min), an effect restored by CSN resection and maintained until 9 weeks after surgery. Ageing did not alter glucose tolerance in CTL animals, but HFHSu diet induced glucose intolerance (AUC HFHSu before diet=21778±686mg/dl*min; AUC HFHSu 44weeks diet =28112±2035mg/dl*min, p<0.05), an effect decreased by CSN resection (AUC HFHSu 9weeks after surgery =24392±558mg/dl*min). HFHSu diet did not exacerbate ageing-induced hyperinsulinemia (CTLOLD=6.22±0.08mg/l; HFHSuOLD=6.33±0.14mg/l), an effect unaltered by CSN resection (HFHSu 9weeks after surgery =6.32±0.53mg/l). HFHSu diet increased significantly epididymal, perienteric and perinephric fat, an effect that was not modified by CSN resection. Ageing decreased TH in the CB by 49.05% (p<0.01), an effect that was not modified by the CSN resection. Ageing and long-term HFHSu diet consumption did not alter GFAP expression in the CB. In conclusion, long-term hypercaloric consumption in old animals did not modify ageing-induced insulin resistance, while exacerbates glucose intolerance, effects that were restored and ameliorated by CSN resection, respectively. We suggest that modulation of CB activity can be important in ageing-induced insulin resistance as well as in ageing-induced metabolic dysfunction exacerbated by diet.