Objective To study the molecular signaling pathway of aspirin in recurrent spontaneous seizures in epileptic rats. Methods In 80 SD rats， 75 rats were randomly divided into 5 groups， the control group（ C group）； the epilepsy group（ S group）： epilepsy induced by pilocarpine； epilepsy + lentivirus transfection group（ ST group）： after hippocampal injection of shRNA lentiviral transfection［ silence phosphatidylinositol kinase（ PI3K） the subunit p85］； the epilepsy + aspirin group（ SA group）： intraperitoneal injection of aspirin 20 mg/kg； the epilepsy + rapamycin group（ SR group）： intraperitoneal injection of rapamycin 6 mg/kg. The remaining 5 rats were assigned to test group for validation of the lentivirus transfection. Two weeks after modeling， the frequency and time of seizures in rats， and the level of the hippocampal inner cyclooxygenase-2（ COX-2）， interleukin 1β （IL-1β）， p85 subunit of PI3K（ p85）， protein kinase B（ Akt）， ribosomal protein S6 kinase（ p70S6K） and microtubule associated protein 2（ MAP2） were tested. Immunohistochemical staining was used to detect the expression of p70S6K in the hippocampus of rats in each group. Results The time and frequency of seizures in S group were significantly higher than those of SA， SR and ST group（ P＜0.05）， and there was no significant difference among the three intervention groups（ P＞0.05）. The levels of COX-2， IL-1β， p85， Akt， p70S6K and MAP2 protein in S group were significantly higher than those of C group（ P＜0.05）， and the level of p85， Akt， p70S6K， MAP2 in ST and SR group were lower than those in the S group（ P＜0.05）. The level of COX-2， IL-1β， p85， Akt， p70S6K and MAP2 were significantly lower than that of S group（ P＜0.05）， and there was no significant difference of p85， Akt， p70S6K and MAP2 between SA and SR group（ P＞0.05）. Conclusions Aspirin may treat recurrent spontaneous seizures in epileptic rats by inhibiting the PI3K/Akt/mTOR pathway and the expression of MAP2. 【Key