Hypoglycaemia (HG) evokes a highly integrated counter-regulatory response in order to restore normal blood glucose levels1. HG also stimulates a carotid body-mediated hyperpnoea via an increase in peripheral CO2 sensitivity, thus enabling normocapnia to be maintained despite the increased metabolism2. The present study aimed to investigate whether HG changes the pattern of ventilation evoked by hypercapnia and also whether HG modulates the response to hypoxia in a similar manner. Whole body plethysmography (WBP) was used to measure ventilation in air, acute hypoxia (10% O2) and hypercapnia (8% CO2) in 7 conscious male Wistar rats. Ventilatory responses were measured both in normoglycaemia (NG) and after HG was induced by insulin (1.5 iU kg-1 ip). All animals had free access to food and water until they were fasted for 8 hours prior to experiments. Blood glucose levels, sampled by tail prick, tended to be lower after fasting but not significantly (8.0±0.8 vs 6.8±0.5 mmol l-1). NG hypercapnia and hypoxia increased ventilation (VE) from 100±9 to 265±32 ml min-1 and from 104±13 to 223±21 ml min-1 respectively. Insulin induced a significant HG (3.8±0.5 mmol l-1). HG increased the response to hypercapnia (ΔVE from 165±37 to 232±51 ml min-1) by having a greater effect on tidal volume (ΔVT 0.65±0.14 vs 0.99±0.27 ml). During HG, hypercapnic TE was reduced to a similar level as seen in NG (185±21 vs 200±29 ms). In contrast, the decrease in TE in hypoxia was not affected by HG. Both hypercapnia and hypoxia increased the TI:TE ratio (from 0.58±0.06 to 0.91±0.10 and 0.58±0.05 to 0.78±0.08 respectively). Only the magnitude of the hypercapnia-induced increase was dependent on glycaemic state. HG induces changes in baseline ventilation but also interacts with the pattern of the ventilatory response to hypercapnia. This is not the case during hypoxia. Central glucose sensors located within hypothalamic and medullary nuclei1, may have the potential to interact with respiratory control to modulate the pattern of response to CO2 during HG, particularly influencing expiratory drive. The dependency of the increase in TI:TE on blood glucose levels during hypercapnia may reflect the coordinated neuroendocrine responses seen during the counter-regulatory response to HG, allowing ventilation to be matched to the increased metabolic rate.