Background/Aims: Previous in vitro experiments have demonstrated the immunomodulatory functions of mesenchymal stem cells derived from induced pluripotent stem cells (iPSC-MSCs) in brain injury. We have tried to further understand these functions by investigating the neuroprotective effects of iPSC-MSCs in a rat model of cardiac arrest (CA). Methods: CA was induced in adult Sprague-Dawley rats by transcutaneous electrical epicardium stimulation. The rats were divided into four groups. In a separate cohort of sham operation animals, iPSC-MSCs or PBS was infused via the femoral vein after restoration of spontaneous circulation. Survival was evaluated every 2 h until 24 h after CA. Markers of classically activated macrophages (M1) and alternatively activated (M2) macrophages were assessed by qPCR and western blot analysis, and the gene expression profiles of the macrophages were studied in order to identify differentially expressed proteins. Results: The 24-h survival rate was significantly different between the CPR group and iPSC-MSC group (P = 0.033). Additionally, a significant number of mRNAs were differentially expressed between the iPSC-MSC and PBS group. Compared with the sham operation group, both M1(27/29) and M2 (2/29) mRNAs showed a significant increase in expression in the CPR group, while only M2 (22) mRNAs showed a significant increase in expression in the iPSC-MSC group. Western blotting analysis showed that the expression of Arg-1 and CD14 (M2 macrophage markers) was increased in the iPSC-MSC group (P < 0.05), while CD86 and iNOS (M1 macrophage markers) expression was increased in the CPR group (P < 0.05). Conclusion: IPSC-MSCs, which play a key role in immunomodulation, downregulate the level of M1 macrophages and upregulate the level of M2 macrophages after CA.