Orexin plays an important role in regulating respiration.The airway function is predominantly controlled by the vagal nerve which centrally originates from the airway vagal preganglionic neurons (AVPNs) in medulla.The role of orexin in the activity of AVPNs is not known.in present study, the effects of orexin-A on the amino acidergic transmission and the excitability of inspiratory-activated AVPNs were investigated via patch-clamp techniques in brainstem slices of newborn rats.The central effects of orexin-A on the lung function were explored in 14-20-day-old rats using a lung function analyzer.Orexin-A (100 nmol/L) significantly increased the frequency of both glutamatergic spontaneous excitatory postsynaptic currents and GABAergic and glycinergic spontaneous inhibitory postsynaptic currents, but none of the amino acidergic miniature postsynaptic currents were affected by orexin-A.Orexin-A (100 nmol/L) induced depolarization and stimulated the firing frequency in inspiratoryactivated AVPNs.Centrally applied orexin-A (0.5 nmol) significantly increased the inspiratory and expiratory resistance and decreased dynamic compliance (Cdyn).The results suggested that orexin regulates airway resistance and Cdyn via exciting AVPNs.The abnormal upregulation of orexin might partly account for the dyspnea in chronic obstructive pulmonary disease.