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Mesenchymal stem cells (MSCs) are multipotent cells beneficial in regenerative medicine and tissue repair. The therapeutic potential of MSCs for inflammatory diseases and conditions is partly due to secreted exosomes. Exosomes are one group of extracellular vesicles with 50–150 nm in diameter. They can carry numerous molecules and introduce them to the recipient cells to produce various biological effects. Macrophages are classified into M1 and M2 subtypes based on their activation states. M1 macrophages release pro-inflammatory factors like tumor necrosis factoralfa (TNF-α), interleukin1alfa (IL-1α), interleukin1beta (IL-1β), interleukin6 (IL-6), C-X-C motif chemokine ligand 9 (CXCL9), and C-X-C motif chemokine ligand 10 (CXCL10), while M2 macrophages secrete anti-inflammatory mediators including interleukin10 (IL-10), transforming growth factor beta (TGF-β), C-C motif chemokine ligand 1 (CCL1), C-C motif chemokine ligand 17 (CCL17), C-C motif chemokine ligand 18 (CCL18), and C-C motif chemokine ligand 22 (CCL22). This review summarizes the effect of MSC-derived exosomes in the polarization of M2 macrophages, which their anti-inflammatory and immunomodulatory properties are potentially effective in inflammation diseases and conditions such as central nervous system (CNS) diseases, autoimmune diseases, inflammatory bowel disease, cardiomyopathy, graftversushost disease, kidney, liver, lung, and skin injuries.