Abstract: The relation between Ca²⁺/CaM PK II activity and excitatoxicity was studied in an in vitro model of rat hippocampal slices.The slices were exposed to 50～200 μmol·L^-1 glutamate or 25～100 μmol·L^-1 NMDA and glucosefree Krebs buffer for 30 min after being recovered to normal conditions by 2 hours of incubition with standard Krebs buffer. The results showed that inhibition of Ca²⁺/CaM PK II activity in rat hippocampal slices was induced by exogenous EAA(glutamate or NMDA), and Ca²⁺/CaM PK II activity values decreased to 50.1% and 44.7% of control at 200 μmol·L^-1 glutamate and 100 μmol·L^-1 NMDA, respectively; MK801, but not DNQX, antagonized EAAinduced inhibition of Ca²⁺/CaM PK II activity. When the slices were pretreated with MK801 prior to exposure to 200 μmol·L^-1 glutamate or 100 μmol·L^-1 NMDA, the Ca²⁺/CaM PK II activity values were 91.5% and　96.7%,respectively. The changes of extracellular Ca²⁺ or Mg²⁺ concentration influenced Ca²⁺/CaM PK II activity of the slices exposed to exogenous glutamate; Ca²⁺/CaM PK II activity values in the presence of extracellular Ca²⁺ was lower than that in the absence of extracellular Ca²⁺,　and it changed from 501% of control (presence of Ca²⁺) to 64% of control (absence of Ca²⁺)　at 200 μmol·L^-1 glutamate, but Ca²⁺/CaM PK II activity values in the presence of extracellular Mg²⁺ was higher than that in the absence of extracellular Mg²⁺,　and it changed from 50.1% of control(presence of Mg²⁺) to 36.6% of control (absence of Mg²⁺) at 200 μmol·L^-1 glutamate. The results suggest that NMDA receptor may be involved in excitotoxicityinduced inhibition of Ca²⁺/CaM PK II activity.