【Abstract】 Objective To explore the protective effect and mechanism of Na+/H+ exchange inhibitor HOE642 in cardiopulmonary resuscitation (CPR) in rats. Methods The suffocating cardiac arrest and resuscitation model was establish tin rats. 24 SD rats were divided into the control group (group S), single drug group (group S + H), injury group (N group) and HOE642 group (N + H group). After receiving different treatments, the opening level of mitochondrial permeability transition pore (mPTP), the function of mitochondria and the level of oxidative stress, the pathological evaluation of brain tissue and specific marker of ischemiareperfusion injury after CPR were detected in each group. Results Compared with N group, the degree of openness of mPTP, the levels of apoptotic markers, the productions of oxidative stress and the content of specific marker of cerebral ischemiareperfusion injury were significantly decreased in N+H group (P＜001). Compared with N group, the functions of mitochondrial complexes in N+H group increased significantly(P＜001). Conclusion The combined use of HOE642 in CPR after cardiac arrest could apparently reduce the opening of mPTP, improve the functions of mitochondria complexes in brain cells, promote the recovery of energy metabolism, alleviate the cerebral ischemiareperfusion injury and reduce the occurrence of apoptosis and necrosis in brain cells.