Objective To explore the effects of mild hypothermia combined with ifenprodil on the survival of neuronal and translocation of apoptosis inducing factor (AIF) following global cerebral ischemia-reperfusion to understand the mechanism of combination in cerebral resuscitation. Methods Eighty male SD rats were randomly divided into 5 groups of sham (I),model (Ⅱ), ifenprodil (Ⅲ), mild hypothermia (Ⅳ) and ifenprodil plus mild hypothermia (V) (n = 16 each). Group I completed all procedures except for ventricular fibrillation (VF) and cardio pulmonary resuscitation (CPR). For groups Ⅱ and V,the model of global cerebral ischemia-reperfusion was established and VF induced with transoesophageal cardiac pacing ; groups Ⅲ and V received by an intraperitoneal injection of ifenprodil immediately after reperfusion and other groups had an equal volume of distilled water. Rectal temperature was cooled down to (32 1) ℃ in groups Ⅳ and V by rubbing body surface with ethanol in 10 min after reperfusion and maintained 4 hours continuously while other groups at (37 1) ℃. In hippocampal CA1 region at 24 hours after reperfusion, the pathomorphological changes and quantity of pyramidal cells were detected with hematoxylin and eosin staining, nuclear translocation of AIF was shown with immunofluorescence technique and the nuclear expression level of AIF was measured with Western blot. Results Compared with group I (75. 0 3. 2),the number of pyramidal cells decreased in other groups (P <0. 05) ; compared with group Ⅱ (36. 0 1. 2),the number increased in group Ⅲ(46. 81.3),Ⅳ(49. 0 2. 7) and V (61. 3 2. 60)(P <0. 05). In particular, cell count increased significantly in group V (P < 0. 05). Compared to group I,the transloctation of AIF form mitochondria to nucleus was detected in other groups ; compared with group I (0. 022 0. 003),the expression level of AIF in the nucleus was higher in other groups (P < 0. 05). Compared with group II (1. 020 0. 029),the expression levels of AIF in groups Ⅲ(0. 870 0.016),Ⅳ(0. 820 0. 050)and V (0. 550 0. 050) were lower (P <0. 05). And it decreased significantly in group V (P < 0. 05). Conclusion Mild hypothermia plus ifenprodil may alleviate neuronal damage after global cerebral ischemia/reperfusion injury through mitigating its proapoptotic role after AIF translocation.