Abstract: Objective To investigate the role of JNK3 on neuroprotective effect of Hypothermia in the CA1 region of the adult rat after ischemia-reperfusion. Method Models with cerebral ischemia-reperfusion were induced using four-vessel occlusion and received 10 min ischemia. Rats were randomly divided into several groups, including sham-operation, ischemia-reperfusion, Hypothermia pretreated ischemia-reperfusion, SP600125 pretreated ischemia-reperfusion and Vehicle pretreated ischemia-reperfusion. Histological assessment of neuronal damage in the CA1 field was performed via Staining with Toluidine blue. Western blotting was operated to detect expression of JNK3 and c-jun. Results In the CA1 field, both groups of Hypothermia pretreated and SP600125 pretreated, not only ischemia-reperfusion injury was alleviated, but also expressions of p-JNK3 and p-c-jun were down-regulated, compared to ischemia-reperfusion only group. Conclusions Hypothermia inhibits post-ischemic cell death in region of CA1 by down-regulated phosphorylation of JNK3 and its downstream effectors.