To investigate the intracellular mechanism that interleukin-1β (IL-1β) facilitates epileptic seizure and neuronal damage, the effect of IL-1β alone or IL-1β plus glutamate (Glu) on the intracellular free calcium ([Ca2+]i) of single cultured hippocampal neuron was examined by using EPC-9 light-electricity measurement system. The results showed that IL-1β of different concentrations (5 × 103 U/L, 10 ×103 U/L, 20×103 U/L, 30×103 U/L, 50×103 U/L, 100×103 U/L) failed to affect the neuronal [Ca2+]i, but IL-1β could facilitate the augmentation of neuronal [Ca2+]i induced by Glu in a dose-dependent pattern. MK-801 inhibited the effect of Glu on [Ca2+]i, and also inhibited the effect of IL-1β on [Ca2+]i induced by Glu, while verapamil did not influence the effect of Glu or IL-1β. It is concluded that IL-1β, as a neuromodulator, can facilitate the activation of NMDA receptor by Glu, induce the increase of intracellular calcium, which enhances the excitement of neuron.