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Microglia are the first line of defense in the central nervous system. Microglial functions are largely dependent on their pro-inflammatory (M1-like) or anti-inflammatory (M2-like) phenotype. Modulating neuroinflammation <jats:italic>via<\/jats:italic> targeting microglia polarization toward anti-inflammatory phenotype might be a novel treatment for ischemic stroke. Mesenchymal stem cells (MSC) and MSC-derived extracellular vesicles (MSC-EVs) have been demonstrated to modulate microglia activation and phenotype polarization. In this review, we summarize the physiological characteristics and functions of microglia in the healthy brain, the activation and polarization of microglia in stroke brain, the effects of MSC\/MSC-EVs on the activation of MSC <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, and possible underlying mechanisms, providing evidence for a possible novel therapeutics for the treatment of ischemic stroke.<\/jats:p>","DOI":"10.3389\/fneur.2022.1073958","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T04:58:00Z","timestamp":1674017880000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Modulatory effects of mesenchymal stem cells on microglia in ischemic 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