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Objective Recent studies have shown that abnormal activation and secretion of microglia(MG) were observed in the occurrence and development of a large number of neurodegenerative diseases such as Parkinsons disease (PD), Alzheimers disease (AD).Our previous research have also confirmed that the close relationship of MG and epilepsy.However, the cellular basis of epilepsy, especially the precise mechanisms of activated MG on neuronal excitability are not thoroughly elucidated.Methods Primary microglia was cultured and three kinds of microglial conditioned medium were collected: untreated microglial conditioned medium (UT-MCM), KA-activated microglial conditioned medium (KA-MCM), minocycline antibody pre-treated KA-MCM (MC + KA-MCM).HPLC and Patch-clamp were applied to evaluate the effects of kainic acid (KA)-activated MG and cytokines production in the development of epilepsy and its related mechanisms in vitro or in vivo.Results Intracerebroventricular injection of rat with the above-mentioned different conditioned medium respectively, (1) Behavior observation: UT-MCM rats showed no obvious seizure activity; KA-MCM rats showed seizures of grade Ⅲ-Ⅳ; MC + KA-MCM rats showed seizures of grade Ⅰ-Ⅱ.(2) Patch-clamp results showed that: the current amplitude and current density in KA-MCM group were significantly higher than those in UT-MCM group (P < 0.01); after IL-1β antibody pretreatment in KA-MCM, the current amplitude and current density were declined, but still higher than those in UT-MCM group (P < 0.01).(3) HPLC results showed that: the secretion of Glu in KA-MCM group was significantly increased and GABA secretion was obviously decreased when compared with UT-MCM group (P < 0.01).While pretreated KA-MCM with minocycline, Glu secretion was decreased and GABA secretion was increased (P < 0.05).Microglial inhibitor minocycline can reverse the above-mentioned effects.Conclusion Bioactive substances from activated microglia can induce the occurrence of epilepsy, the mechanisms are related to the enhancement of neuronal excitability and neuronal calcium influx and cytokines may be one of the important intermedia in this process.