Background: The carotid bodies (CB) are peripheral chemoreceptors that classically sense arterial O2, CO2 and pH levels (Gonzalez et al., 1994). In addition to hypoxia, in the last decade a role for the CB has a role in the control of energy homeostasis (Koyama et al., 2000; Wehrwein et al., 2010) has emerged. Recently, our group has described that insulin triggers CB activation and that carotid sinus nerve resection prevents the development of insulin resistance, suggesting the involvement of the CB in the regulation of peripheral insulin sensitivity (Ribeiro et al., 2013). However the mechanism (s) and the effectors involved on CB insulin action remains unclear. It is known that Kv1.3 channels are an important player on insulin pathways as they are involved in insulin signaling in central nervous system and periphery (Fadool et al., 2000; Xu et al., 2004). The hypothesis herein tested is that Kv1.3 channels are the effectors of insulin signaling in the CB being the phosporylation of Kv1.3 channels, one of the potential mechanisms by which insulin modulates CB activity. Methods: Experiments were performed in CB dissociated cells isolated from Wistar rats. Rats were anaesthetized with sodium pentobarbital (60 mg/kg-1 i.p), tracheostomized and the carotid arteries were dissected and the CB isolated to subsequently dissociate of CB cells. The effects of insulin and specific blockers of Kv1.3 channels, Margatoxin (MgTx) (1-10nM) and ShK-Dap22 (100pM) have been studied on voltage-activated K+-currents by whole-cell voltage-clamp recordings. Also, the expression of Kv1.3 channels and its phosphorylation in response to insulin was evaluated by immunocytochemistry and western blot, respectively. Finally, the effect of insulin and MgTx (10n M) on dopamine release from the CB has been evaluated. Results: We have found that insulin promotes a decrease in K+-current in CB type I cells and that MgTx and ShK-Dap22 mimic insulin action. Also, the reduction of the effect of insulin in K+-currents with increasing concentrations of MgTx demonstrates the involvement of Kv1.3 channels in this mechanism. Immunocytochemical studies detected the presence of Kv1.3 channels in CB type I cells and western blot the presence of the protein in the whole CB. When trying to unravel how insulin receptors interact with Kv1.3 channels, we have found that insulin was able to modulate the Kv1.3 channels activity through phosphorylation at residue tyrosine 135. Additionally, MgTx was capable of blocking the dopamine evoked-release by insulin in the whole-CB. Conclusion: We demonstrate for the first time that Kv1.3 channels are functional in CB and those channels mediate insulin action in the CB. Modulation of their activity may serve as a novel therapeutic target for insulin resistance