Abstract: Mesenchymal stem cells are a potential therapeutic candidate for cerebral infarction due to their anti-inflammatory proprieties. However, ensuring the engraftment of sufficient cells into the affected brain area remains a challenge. Herein, magnetic targeting techniques were used for the noninvasive transplantation of a large number of cells noninvasively. Mice subjected to permanent middle cerebral artery occlusion surgery were administered mesenchymal stem cells labeled or not with iron [email protected] nanoparticles by tail vein injection. Iron [email protected] particles were characterized by transmission electron microscopy, and labeled mesenchymal stem cells were characterized by flow cytometry and their differentiation potential was assessed in vitro . Following the systemic injection of iron [email protected] mesenchymal stem cells into permanent transient middle cerebral artery occlusion-induced mice, magnetic navigation increased the MSCs localization to the brain lesion site and reduced the lesion volume. Treatment with iron [email protected] mesenchymal stem cells also significantly inhibited M1 microglia polarization and increased M2 microglia cell infiltration. Furthermore, western blotting and immunohistochemical analysis demonstrated that microtubule-associated protein 2 and NeuN levels were upregulated the brain tissue of mice treated with iron [email protected] mesenchymal stem cells. Thus, iron [email protected] mesenchymal stem cells attenuated brain injury and protected neurons by preventing pro-inflammatory microglia activation. Overall, the proposed iron [email protected] mesenchymal stem cells approach may overcome the major drawback of the conventional MSCs therapy for the treatment of cerebral infarction.