Leptin is a pleiotropic hormone synthesized and secreted mainly by white adipose tissue. It is involved in metabolism and energy balance and cardiovascular and respiratory control, acting as a potent stimulant of breathing in the central nervous system. Recently, the expression of the leptin receptor in the lungs and the carotid body (CB) has been reported and therefore additional peripheral actions of leptin on the respiratory system have been suggested. This finding has been associated to a physiological role of circulating leptin in the regulation of CB function and to the pathogenesis of respiratory disorders. Based on these reports, we have tried to analyze the impact of leptin on the hypoxic ventilatory response (HVR) and on the hypoxic elicited CB response in animal models of two respiratory disorders, obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS). The experiments were carried out on adult male Wistar rats (250-400 g), randomly divided into four groups: Control (C, air breathing, standard diet; n=16), chronic intermittent hypoxia (CIH; 5%O2 40s, 80 s 21%O2, 8h/d, 21 d, standard diet; n=16), high-fat diet induced obesity (O; 21 d, n=16) and CIH/Obesity combination (OIH, both treatment, 21d; n=16), analyzing plasma leptin levels, breathing parameters and effects of leptin on the basal and hypoxia elicited CB secretory response, in anaesthetized rats (sodium pentobarbital, 60 mg/Kg, i.p.) of the four group. At the end of experiments, rats were euthanized by an intracardiac overdose of pentobarbital. We verified that exposure to HCI did not produce significant ventilatory changes, in spite of CB sensitization, that could be related to low plasma leptin level observed (24 ± 10 ng /mL). Diet induced obesity (O) and IH combined treatment (OIH) produced basal hypoventilation and decreased HVR to 7%O2 (20% decrease vs control rats), with a restrictive respiratory pattern (increased respiratory rate) and very high plasma leptin levels in both conditions (216 ± 41 and 178 ± 37 ng/mL, respectively). In isolated control CB, a high acute dose of leptin (250 ng /mL), but not low doses, potentiated the hypoxia induced catecholamine (CA) release by 190%, while not affecting the CA basal output. Conversely, the effect of leptin on the hypoxic response of CB was abolished after CIH, O or OIH exposure of rats. We conclude that in rats, the effect of leptin on ventilation could also be mediated by peripheral chemoreceptors, enhancing the CB response to hypoxia. Rat exposure to CIH and high-fat diet, blunts leptin effect on CB activity by different mechanism. Whereas the diet induced obesity, with very high levels of circulating leptin, could abolish the leptin effect on CB by a leptin resistant state, CIH blunts leptin effects with low plasma leptin levels.