Transplantation of various types of stem cells as a possible therapy for stroke has been tested for years and the results are promising. Recently, most researchers are inclined to assume that the therapeutic effect of stem cell therapy is based on the mechanism of paracrine action associated with the secretion wide set of regulatory proteins. The aim of this study was to evaluate therapeutic effects of iPSC-derived glial progenitor cells conditioned medium in the rat middle cerebral artery occlusion model of the ischemic stroke. We showed that intra-arterial administration of glial progenitor cells conditioned medium promoted faster decrease of neurological deficit compared to the control group. Moreover, expression of gap43, bax, and tnfa genes involved in neuritogenesis, apoptosis and neuroinflammation was altered. However, no significant enhanced reduction of the infarct volume was registered. Our results demonstrated that administration of glial progenitor cells conditioned medium induced functional recovery after experimental stroke and may affect brain plasticity. © 2020, Human Stem Cell Institute. All rights reserved.