Microglia are constantly surveying their microenvironment and rapidly react toimpairments by changing their morphology, migrating toward stimuli and adopting geneexpression profiles characterizing their activated state. The increased expression of theM2-like markerMannose receptor 1(Mrc1), which is also referred to as CD206, inmicroglia has been reported after M2-like activationin vitroandin vivo.Mrc1is a 175-kDa transmembrane pattern recognition receptor which binds a variety of carbohydratesand is involved in the pinocytosis and the phagocytosis of immune cells, includingmicroglia, and thought to contribute to a neuroprotective microglial phenotype. Herewe analyzed the effects of TGFβsignaling onMrc1expression in microgliain vivoandin vitro. Using C57BL/6 wild type andCx3cr1CreERT2:R26-YFP:Tgfbr2fl/flmice-derivedmicroglia, we show that the silencing of TGFβsignaling results in the upregulationofMrc1, whereas recombinant TGFβ1 induced the delayed downregulation ofMrc1.Furthermore, chromatin immunoprecipitation experiments provided evidence thatMrc1is not a direct Smad2/Smad4 target gene in microglia. Altogether our data indicatethat the changes inMrc1expression after the activation or the silencing of microglialTGFβsignaling are likely to be mediated by modifications of the secondary intracellularsignaling events influenced by TGFβsignaling.