Our lab and others have previously demonstrated that leptin resistance impairs insulin sensitivity in the hypothalamus, providing a possible link between obesity and type II diabetes. Conversely, insulin resistance is thought to impair leptin actions in the hypothalamus, providing the basis for the emerging hypothesis that the central regulation of metabolic function relies on intracellular cross-talk between hypothalamic insulin and leptin signalling. To further explore this hypothesis, we compared measures of long-term energy balance as well as glucose tolerance and acute leptin signalling between neuron-specific insulin receptor knockout (CamKIIα-IRKO) and littermate control (CON) mice. Despite the complete absence of hypothalamic insulin responsiveness (insulin-induced phospho-AKT) in the CamKIIα-IRKO mice, no evidence of leptin resistance was observed. Firstly, unlike leptin deficient (ob/ob) and leptin resistant (db/db) mice which display profound obesity and glucose intolerance, only a mild body weight phenotype was observed in the CamKIIα-IRKO vs. CON male (37.5 ± 1.2 g vs. 34.3 ± 1.1 g, P = 0.067) and female (34.6 ± 1.2 g vs. 31.0 ± 0.8 g, P = 0.023) mice, which was due to increased abdominal adiposity in female (8.7 ± 0.6% vs. 6.1 ± 0.6%, P < 0.01) but not male (7.5 ± 0.6% vs. 7.3 ± 0.4%, P = 0.88) mice. Furthermore, male and female CamKIIα-IRKO mice exhibited normal fasting blood glucose concentration and likewise exhibited normal glucose tolerance in response to an acute glucose challenge (1 g/kg). Lastly, in response to acute leptin treatment (1 mg/kg), no differences in STAT3 activation (phospho-STAT3) were observed in any hypothalamic region examined between CamKIIα-IRKO and CON mice. These data suggest leptin sensitivity is preserved in the absence of hypothalamic insulin receptor signalling, which does not support the emerging belief that intracellular cross-talk between insulin and leptin signalling is required for the central regulation of metabolic function.