Objective To investigate the optimal timing of mannitol intervention in cerebral ischemia-reperfusion injury.Methods Thirty-six mice were randomly divided into six groups (n=6):The sham operation group (group A),the control group (ischemia-reperfusion injury group,group B),aud the mannitol intervention group at the time of 0 min,30 min,1 h and 1.5 h after reperfusion (group C,D,E,F).Taken the brain twenty-four hours after ischemia-reperfusion injury.Morphological changes,viability and degradation of cells in the area of CA1 of hippocampus were studied in each group.Results In the experimental group with mannitol intervention immediately after reperfusion,most hippocampal pyramidal cells remained normal morphology with intact structures and no intercellular edema was observed.The amount of viable cells was (22.0±1.1) per 100 μm which was not significantly different from that of the sham operation group (23.0±0.9).The incidence of cell degradation was 8.17%,which was significantly lower than that of the control group (40.17%,P<0.05).The cell degradation difference between the experimental group and sham operation group(7.33%) was not significant(P>0.05).Mannitol intervention beginning over 30 min after reperfusion failed to alleviate neuron injury.Conclusion After the establishment of blood pressure gradient,inverted osmotic pressure gradient by means of prompt mannitol intervention at the early stage of cerebral ischemia-reperfusion can effectively prevent the formation of intracellular edema and avoid the consequent irreversible cellular injury.Mannitol intervention beginning over 30 min after reperfusion was proved ineffective. Key words: Cerebral ischemia/reperfusion injury; Mannitol; Mice