Cardiac arrest and global cerebral ischemia-reperfusion injury after cardiopulmonary resuscitation (CPR) are common pathological conditions in critically ill patients, with high mortality and disability rates. Currently, the conventional asphyxia method is commonly used to establish a brain injury model after CPR. However, it has a low resuscitation success rate and postoperative survival rate. Therefore, a modified asphyxia model of cardiac arrest and global cerebral ischemia-reperfusion injury after CPR was established and compared it with the conventional asphyxia method to evaluate its advantages. Sprague Dawley(SD) rats were randomly divided into a conventional group and a modified group. The conventional asphyxia method and the modified asphyxia method were used to establish the models, respectively. The resuscitation success rate and 24-hour survival rate were observed. Neurological deficits were assessed using neurological deficit scores. Hematoxylin-eosin staining was used to observe pathological changes in brain tissue. Transmission electron microscopy was used to examine neuronal ultrastructure. Western Blot analysis was performed to detect inflammatory, oxidative stress, and apoptotic markers. The results show that compared with the conventional asphyxia method, the modified asphyxia method has a higher resuscitation success rate and 24-hour survival rate. No significant differences are observed in brain injury, inflammation, oxidative stress, and apoptosis between the two methods. The modified asphyxia method meets the requirements for studying global cerebral ischemia-reperfusion injury.