Abstract: Objective:To clarify the neurotransmitter mechanism of protective effect of isoflurane preconditioning on global cerebral ischemia and if the protective effect has the character of time limitation on cerebral ischemia.Methods:The rats were anesthetized with 1.0MAC of isoflurane in air 1h for 5 days（1/per day） as the method of preconditioning.The wakeful model of global cerebral ischemia and reperfusion（4-V0） was set up 2 days before ischemia.The microdialysis samples were collected and BIS was recorded after reperfusion.The recovery of right reflection was observed after ischemia and the motor function was investigated.All viable and apoptotic neurons were counted and the % apoptotic neuron was calculated.Results:The BIS and right reflection of preconditioning groups was better than control groups after ischemia of 10 and 15 min.The change of glutamate concentration in hippocampus showed no significant difference between two groups.Preconditioning with isoflurane resulted in significant better total motor performance compared with control groups after ischemia of 15 min.The viable neurons and apoptotis rate in the CA1 sector of hippocampus of preconditioning groups were significantly better compared with control groups after ischemia of 10 and 15 min;but there was no difference between two groups after 20 min ischemia.Conclusions:Isoflurane preconditioning has protective effect to global cerebral ischemia-reperfusion injury,but it has limited ability for serious ischemia-reperfusion;The protective effect appears to be no related to decrease the concentration of glutamate transmitter during wakefulness and ischemia-reperfusion.