Adenosine triphosphate (ATP) is released from glial cells in the central nervous system, and induces plastic changes in synaptic transmission. Despite the recent progress in terms of the roles of purinergic receptors in cerebrocortical excitatory synaptic transmission, their contribution to inhibitory synaptic transmission has been unknown. Setting the ultimate goal to clarify the role of ATP in neuroplastic changes in inhibitory synaptic transmission in the cerebral cortex, this study aimed to elucidate the effects of ATP and α,β-methylene ATP (αβmATP), a selective agonist of P2X receptors (P2XR), on inhibitory synaptic transmission in the insular cortex (IC). We performed multiple whole-cell patch-clamp recordings from pyramidal cells (PYR) in IC of the VGAT-Venus transgenic rats. Administration of αβmATP (100 μM) increased the amplitude of unitary IPSCs (uIPSC). Interestingly, αβmATP increased the amplitude of miniature IPSCs (mIPSCs), which sustained even after washout of αβmATP. The P2XR-dependent potentiation was blocked by intracellular application of an NMDA receptor (NMDAR) antagonist, MK801. These results suggest that the activation of the P2XR-NMDAR pathway induces long-term potentiation of IPSCs in the IC.