GABA is the main inhibitory neurotransmitter in the central nervous sys- tem. Leptin, the obese gene peptide, is involved in the regulation of feed- ing behavior and energy balance. The present study was set to determine the changes of firing rate in the neurons of the preoptic area/anterior hypo- thalamus (PO/AH) in male Wistar rats after administration of leptin, GABAB- agonist baclofen and GABAB-antagonist CGP35348 applied separately or in combinations. In vitro experiments were made on PO/AH neurons by conventional electrophysiological equipment, using brain slice prepara- tion. To trace the changes in neuronal firing rate we used administration in bolus of the experimental substances during constant perfusion of the slice preparation with artificial cerebrospinal fluid (ACSF). The separate bolus injection of leptin as well as GABAB-antagonist CGP35348 produced significant increase of firing rate in rat PO/AH neurons, while the GABAB- agonist baclofen caused a decrease in firing rate. The probable synergy between the effects of leptin and GABAB-antagonist was not occurred. In the opposite, effect of this combination was lower compared to the result of the separate administration. When leptin was applied in combination with GABAB-agonist baclofen neither one of their separate effects ap- peared. The data from this study provide a new point of view concerning the interactions of leptin and GABA. These results are step of understanding the complicate mechanisms involved in the interactions of neurotransmit- ters and neuromodulators in the central nervous system.