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Interleukin\u20104 (IL4) has shown beneficial abilities to re\u2010establish microglial homeostasis in experimental models of CNS traumatic injury, stroke and multiple sclerosis, but its optimal administration system remains uncertain. Here, we show that extracellular vesicles (EVs) released by engineered murine microglia BV2 cells constitutively expressing IL4 induced a faster and enhanced anti\u2010inflammatory phenotype in wild type BV2 cells (as assessed by IL4R downstream signalling), compared with soluble IL4. This effect was blunted by an anti\u2010IL4 antibody, while it was not dampened by knocking out the IL4 receptor \u03b1 subunit in EV\u2010releasing BV2 cells, suggesting that IL4 was localized on the EV surface and did not necessitate to be co\u2010conveyed with the receptor to exert its function. BV2 cells treated with EV\u2010associated IL4, compared with soluble IL4, demonstrated delayed permanence of IL4R in the early endosome, suggesting amplified signalling effects. 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