Increased sympathetic activity is a well-known pathophysiological mechanism in insulin resistance (IR) and hypertension (HT). The carotid bodies (CBs) are arterial chemoreceptors being PO2, PCO2/pH sensors-efectors which upon a decrease in PO2 or a PCO2/[H+] increase, release neurotransmitters that regulate the firing rate in the sensory fibres of the carotid sinus nerve (CSN). CSN activity is integrated in the brain stem to induce a fan of respiratory reflexes aimed, primarily, to normalize the altered blood gases via hyperventilation (Gonzalez et al.1994) and to regulate blood pressure and cardiac performance via sympathetic nervous system activation (Marshall 1994). The CB directly activates the adrenals via increased sympathetic drive and also increases sympathetic vasoconstrictor outflow to muscle, splanchnic, and renal beds (Marshall 1994; Cao & Morrison 2001). Recently, the CB was proposed to be a glucose sensor (Pardal & López-Barneo 2002) and implicated in energy homeostasis control (Koyama et al. 2000). However, to date no studies have anticipated its role in the development of IR. The aim of this work was to investigate the role of the CB in the pathogenesis of IR and HT. Experiments were performed in Wistar rats (200-420 g) of both sexes, aged 3 months. Two diet-induced IR and HT animal models were used: the rat submitted to a high-fat (HF) diet, a model that combines obesity, IR and HT and the rat submitted to a high-sucrose (HSu) diet, a lean model of combined IR and HT. To test the hypothesis that CB activity is increased in IR and HT animal models we compared HF and HSu with control group. To evaluate the contribution of CB to the genesis of IR and HT, bilateral resection of CSN was performed 5 days prior to submitting the animals to standard or hypercaloric diets. These procedures were performed in aseptic conditions under ketamine (30mg/kg)/xylazine (4mg/kg) anaesthesia and brupenorphine (10microg/kg) analgesia. Additionally, rats fed with standard diet were used to investigate if insulin triggers CB activation. All measurements were performed with animals under sodium pentobarbital (60 mg/kg i.p.) anaesthesia. We demonstrated that CB activity was increased in diet-induced animal models of IR and HT. CB-mediated basal ventilation and ventilation in response to ischemic hypoxia were increased in the pathological models tested, as well as the CB chemoreceptor cell function – assessed both as hypoxia induced-release of dopamine and as tyrosine hydroxilase expression. We have also observed that CSN bilateral resection totally prevented diet-induced IR and HT, as well as increased fasting glicemia, fasting insulinemia, free fatty acids and systemic sympathoadrenal overactivity. Moreover, we showed that insulin triggers CB, highlighting a new role for hyperinsulinemia as a stimulus for CB-overactivation. We demonstrated that insulin receptors are present in the CB and that its phosphorylation increases in response to insulin. Additionally, we showed that insulin was capable of initiating a neurosecretory response measured as the increase in intracellular Ca2+ and the release of the neurotransmitters, ATP and dopamine, that is transduced into an increase in ventilation. We propose that CB is implicated in the pathogenesis of metabolic and hemodynamic disturbances through sympathoadrenal overactivation and may represent a novel therapeutic target in these diseases.