Background: The role of miRNAs in macrophage polarization has not been well defined. Results: miR-125a-5p promotes M2, while it suppresses M1 macrophage polarization. Conclusion: miR-125a-5p is an important regulator of the differential activation of macrophages. Significance: Delineation of the role of miR-125a-5p in macrophage polarization provides insights into miRNA regulation of inflammation, tissue repair and tumor progression. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.