Introduction: The medial orbitofrontal cortex is involved in the regulation of feeding and metabolism. Little is known, however, about the role of local glucose-monitoring neurons in these processes, and our knowledge is also poor about characteristics of these cells. Aim: The functional significance of these chemosensory neurons was to be elucidated. Method: Electrophysiology, by the multibarreled microelectrophoretic technique, and metabolic investigations, after streptozotocin induced selective destruction of the chemosensory neurons, were employed. Results: Fifteen percent of the neurons responded to glucose, and these chemosensory cells displayed differential neurotransmitter and taste sensitivities. In acute glucose tolerance test, at the 30th and 60th minutes, blood glucose level in the streptozotocin-treated rats was significantly higher than that in the controls. The plasma triglyceride concentrations were also higher in the streptozotocin-treated group. Conclusions: Glucose-monitoring neurons of the medial orbitofrontal cortex integrate internal and external environmental signals, and monitor metabolic processes, thus, are indispensable to maintain the healthy homeostasis.