Macrophages can be divided into two groups as M1 and M2 phenotype. Our results and other groups revealed that IFN-gamma can up-regulate the IDO expression and differentiate THP-1 cells to M1 phenotype. Therefore we hypothesized that IDO may play potential roles in macrophage differentiation. Interesting, our results indicated that the ectopic IDO increases the expression of M2 markers such as IL-10 and CXCR4 while decreases the M1 markers such as CCR7 and IL-12p35. In contrast, the knockdown of IDO expression in THP-1 cells resulted in increased M1 markers and lower M2 markers. Our results suggested that the expression intensity of IDO modulates macrophages differentiation. These finding support the counter-regulatory role for IDO with regarding to the polarization of macrophages to restrain excessive or inappropriate immune activation in inflammatory or tumor microenvironment It throws new light on the mechanisms about the immunosuppressive effect of IDO in tumor or inflammatory diseases. (C) 2014 Elsevier Inc. All rights reserved.