Dysmetabolic features like insulin resistance, dyslipidemia and obesity are characterized by autonomic dysregulation. Recently, a new line of research linking autonomic dysfunction and metabolic diseases has emerged with the report that the carotid bodies (CBs) are involved in the development of insulin resistance (1,2). The CBs are arterial chemoreceptors that sense changes in arterial blood O2, CO2, and pH levels. Apart from the control of ventilation, the CB has been reported to sense glucose, being implicated in the control of energy homeostasis. We have recently described that CB activity is increased in rodent models of insulin resistance. Additionally, we have shown that selective bilateral resection of the nerve of the CB, the carotid sinus nerve (CSN), prevents the development of diet-induced insulin resistance and hypertension as well as sympathoadrenal overactivity. These results imply that the beneficial effects of CSN transection on insulin action and glucoregulation, are modulated by target-related efferent sympathetic nerves, through a reflex that is initiated in the CBs. Subsequently, we aimed to test if the functional abolishment of CB, through CSN transection, improves insulin action and glucose and lipid homeostasis in prediabetes and early type 2 diabetes animal models. Moreover, bioelectronic medicine, a new treatment modality that modulates signals in peripheral nerves and allows improved precision, personalization and adherence is emerging. Thus, in the present work, we have also investigated the potential of CSN electric neuromodulation as a viable therapeutic strategy to treat insulin resistance and glucose intolerance. Experiments were performed in Wistar rats (200-420 g) of both sexes, aged 8 weeks. Two diet-induced prediabetes animal models were used: high-fat (HF) diet rat, a model that combines obesity, IR and HT and the high-sucrose (HSu) diet rat, a lean model of combined IR and HT. Additionally, an early type 2 diabetes model that combines IR, glucose intolerance, HT and hyperinsulinemia was obtained by submitting the rats to a combined HF/HSu diet for 14 weeks. Pathological animal models have been compared with age-matched controls. Animals were monitored at baseline for IR, glucose tolerance and weight. Following diet protocol dysmetabolic features have been confirmed and the animals have been submitted to unilateral or bilateral CSN transection under ketamine (30mg/kg)/xylazine (4mg/kg) anesthesia and brupenorphine (10µg/kg) analgesia (1). Metabolic parameters have been evaluated weekly in order to determine the effect of CSN resection in these parameters throughout time. To test the impact of continuous reversible electrical block of the CSN on insulin action and glucose homeostasis, we have implanted electrode cuffs at the CSN after 14 weeks of HFHSu diet, under ketamine (30mg/kg)/metedomidine (4mg/kg) anaesthesia and brupenorphine (10 µg/kg) analgesia. After 2 weeks of recovery animals have been submitted to continuous high frequency stimulation during 9 weeks and metabolic parameters have been evaluated. The reversibility of blocking was investigated during 5 weeks after stop high frequency stimulation. At the end of the experimental protocol all the animals have been sacrificed by an overdose of pentobarbitone. We demonstrated that CSN denervation re-established insulin sensitivity, normoglycemia and normoinsulinemia, glucose tolerance, autonomic function and normalized mean arterial pressure in animal models of prediabetes and early type 2 diabetes. Additionally, high frequency stimulation electrical block of the CSN, increased insulin action and restored glucose tolerance in HFHSu rats during the 9 weeks of electrical block. The effect of electrical blocking on the CSN was reversible, since 5 weeks after stop blocking the animals developed again insulin resistance and glucose intolerance. We conclude that modulation of CB positively impacts on insulin action and glucose tolerance and that electrical modulation of CSN may represent a novel therapeutic approach for diabetes.