Hypoxia is a serious stress state. The nervous system is less tolerant to hypoxia, and cell death due to hypoxia is irreversible. With the incidence of cardiovascular disease gradually increasing, the sudden cardiac death rate is additionally increasing. Although cardiopulmonary resuscitation (CPR) is an important development, recovery is frequently poor. In a successful recovery population, similar to 40% of the population was in a vegetative state or subsequently succumbed to their condition, and similar to 20% had brain damage. Therefore, the recovery of the brain is of particular importance in CPR. Immune disorders are one of the major mechanisms of cerebral resuscitation following CPR. Studies have demonstrated that induced pluripotent stem cell-derived mesenchymal stem cells (IPSC-MSCs) have a strong immune regulatory effect during tissue repair and anti-inflammatory effects. IPSC-MSCs may inhibit the inflammatory response by means of the inflammatory reaction network to improve brain function following CPR, although the cellular and molecular mechanisms remain unclear. Macrophages are a bridge between innate immune and specific immune responses in the body; therefore, it was hypothesized that macrophages may be the important effector cell of the role of IPSC-MSCs in improving brain function following recovery of spontaneous respiration and circulation subsequent to cardiopulmonary resuscitation. In the present study, IPSC-MSCs were applied to the oxygen and glucose deprivation (OGD) model. It was observed that intervention with IPSC-MSCs was able to alter the polarization direction of macrophages. The difference in the proportions of M1 and M2 macrophages was statistically significant at 6, 12, 24 and 48 h (P=0.037, P<0.05) in the OGD + IPSC-MSCs group (M1, 33.48 +/- 5.6%; M2, 50.84 +/- 6.9%) and in the OGD group (M1, 83.55 +/- 7.3%; M2, 11.41 +/- 3.2%), and over time this trend was more obvious. The polarization direction of macrophages is associated with the neurogenic locus notch homolog protein 1 (Notch-1) signaling pathway. In conclusion, it was observed that IPSC-MSCs may be associated with altered macrophage polarization, which may be accomplished by inhibiting the Notch-1 signaling pathway.