Hypothalamic and hippocampal neurons in the central nervous system can sense and respond to changes in metabolic signals such as insulin and glucose. GABA (gamma-aminobutyric acid) and its receptors have been shown to have a role in the central control of metabolic homeostasis. The aim of our study was to investigate the insulin effect on GABA-A receptors-mediated inhibition in rat hippocampal CA1 pyramidal neurons. Rat hippocampal slices (P16-P22) were prepared and incubated with low concentration of insulin for 1, 2, and 3 hours. Standard whole-cell recording and quantitative PCR were performed. Insulin incubation regulated both phasic and tonic currents mediated by GABA-A receptors in a temporal manner. PCR results from the CA1 region showed altered mRNA expression of alpha4, alpha5 but not delta GABA-A receptor subunits. Our results suggest that low concentration of insulin potentiates GABA-generated inhibition by modulating both synaptic and extrasynaptic GABA currents.