The three colony-stimulating factors, granulocyte/macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and granulocyte colony-stimulating factor (G-CSF), have been regarded as immunostimulators because of their role in granulocyte and myeloid hematopoiesis and immune function. However, unlike GM-CSF and M-CSF, G-CSF possesses immunosuppressive effects on other immune cells including monocytes/macrophages, dendritic cells, and T lymphocytes when exogenously administered. Given the immunomodulatory effects of exogenous G-CSF, endogenous G-CSF may also play an important role in maintaining local immune homeostasis in tissue in which it is highly and constitutively produced. This review highlights the potential role of G-CSF in immunomodulation and intestinal immune homeostasis. © 2010 IUBMB IUBMB Life, 62(8): 611–617, 2010.