Objective To evaluate the influence of hypothermia to Ca 2+/calmodulin-dependent kinase Ⅱ during global brain ischemia in rats. Methods Fifteen male SD rats were randomly divided into 3 groups: control group (group Ⅰ, n=5), hepothermia group (group Ⅱ, n=5) and reperfusion group (group Ⅲ, n=5). Only sugery was performed without hypothermia and clipping bilateral carotids in group Ⅰ. Ice was used covering head of rats in group Ⅱ to get hypothermia around 32℃, and bilateral carotids were clipped 20 min of ischemia followed by 60 min reperfusion keeping tympanum temperature 32℃. Bilateral carotids were clipped 20 min of ischemia followed by 60 min reperfusion without hypothermia in Group Ⅲ. Brain tissues were saved in three groups after experiments for evaluating Ca 2+/calmodulin-dependent kinase Ⅱ. Results Left tympanum temperature in the group Ⅱ is significantly lower than group Ⅰ during global ischemia and reperfusion(p<0.05). Those are no difference between group Ⅰ and group Ⅲ. The activity of Ca 2+/calmodulin-dependent kinase Ⅱ after 60 min reperfusion in both Group Ⅱ and group Ⅲ was significantly lower than those in the group Ⅰ(P<0.05), which is significantly higher in the group Ⅱ than in the group Ⅲ(P<0.05). Conclusion Hypothermia can increase the activity of Ca 2+/calmodulin-dependent kinase Ⅱ after global ischemia reperfusion. Hypothermia has significant protection during ischemia reperfusion injury.