Experimental evidence suggests glucose modulates gastric functions via vagally-mediated effects. It is unclear whether glucose affects only peripheral vagal nerve activity or whether glucose also modulates vagal circuitry at the level of the brainstem. This study used whole cell patch clamp recordings from neurons of the nucleus of the tractus solitarius (NTS) to assess whether acute variations in glucose modulates vagal brainstem neurocircuitry. Increasing D-glucose concentration induced a postsynaptic response in 40% of neurons; neither the response type (inward vs outward current) nor response magnitude was altered in the presence of tetrodotoxin (TTX) suggesting direct effects on the NTS neuronal membrane. In contrast, reducing D-glucose concentration induced a postsynaptic response (inward or outward current) in 54% of NTS neurons; TTX abolished these responses suggesting indirect sites of action. The frequency, but not amplitude, of spontaneous and miniature excitatory postsynaptic currents (s/mEPSCs, respectively) was correlated with D-glucose concentration in 79% of neurons tested (n=48). Prior surgical afferent rhizotomy abolished the ability of D-glucose to modulate sEPSC frequency, suggesting presynaptic actions at vagal afferent nerve terminals to modulate glutamatergic synaptic transmission. In experiments where EPSCs were evoked via electrical stimulation of the tractus solitarius, EPSC amplitude correlated with D-glucose concentration. These effects were not mimicked by L-glucose, suggesting the involvement of glucose metabolism, not uptake, in the nerve terminal. These data suggest that the synaptic connections between vagal afferent nerve terminals and NTS neurons are a strong candidate for consideration as one of the sites where glucose-evoked changes in vago-vagal reflexes occurs.