OBJECTIVE The aim of this study was to investigate whether the activation of the NR2B phosphrylation participate in the adult seizure susceptibility after prolonged febrile seizures (FS).METHODS FS were induced by exposing rat pups (P8-10) to a hyperthermic chamber (44 ± 2℃) to raise the body temperature with stereotyped behaviors and typical epileptic EEG.Maximal electroshock (MES) or kainic acid-induced seizure models were used to test adult seizure susceptibility.The expression of IL1β, total NR2B and phosphorylated NR2B were measured by Western Blotting.Exogenous I L-1β, interleukin 1 receptor antagonist (IL-1ra) and NR2B antagonist ifenprodil were used.RESULTS We found that: 1, The expression of pTyr1472-NR2B gradually increased and reached a peak at 24h after prolonged FS while the total NR2B had no obvious change.2, IL1 β alone increased the expression of pTyr1472-NR2B, while the IL-1 ra reversed the phosphrylation of NR2B when treated immediately after prolonged FS.3, NR2B antagonist ifenprodil reversed the enhanced susceptibility to MES and KA induced seizures when injected within three days after prolonged FS or IL1β-injection.CONCLUSION Our study indicated that NR2B phosphorylation at Tyr1472, which is regulated by IL1β, is involved in the enhanced seizure susceptibility after prolonged FS.