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Understanding the events that lead to metastasis is critical to develop better interventions for this disease. Alveolar macrophages are potentially involved in priming the lung microenvironment for OS metastasis, yet the mechanisms involved in this process remain unclear. Since extracellular vesicles (EVs) are a known actor in primary tumor development, their potential role in OS metastagenesis through macrophage modulation\u00a0is explored here. The interaction of EVs isolated from highly metastatic (K7M2) and less metastatic (K12) osteosarcoma cell lines is compared with a peritoneal macrophage cell line. An EV concentration that reproducibly induced macrophage migration is identified first, then used for later experiments. By confocal microscopy, both EV types associated with M0 or M1 macrophages; however, only K7M2\u2010EVs are associated with M2 macrophages, an interaction that is abrogated by EV pre\u2010treatment with anti\u2010CD47 antibody. Interestingly, all interactions appeared to be surface binding, not internalized. In functional studies, K7M2\u2010EVs polarized fewer macrophages to M1. 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