Granulocyte colony stimulating factor (G-CSF) plays a key role in the regulation of neutrophil production, function and survival. The G-CSF receptor (G-CSF-R) it most highly expressed by neutrophils and myeloid progenitors, and at lower levels by macrophages and monocytes. Here, we investigated the role of G-CSF and neutrophils in two extensively used models of central nervous system (CNS) autoimmunity both of which have long been described as T cell-mediated - experimental autoimmune encephalitis (EAE) and experimental autoimmune uveoretinitis (EAU).In G-CSF^-/- mice and in WT mice treated with anti-G-CSF monoclonal antibody (mAb), disease severity in both models was dramatically reduced. A mixed population comprising macrophages ,T cells and neutrophils were identified by flow cytometric analysis of the ocular infiltrate in WT mice with EAU. The eyes of G-CSF-deficient and anti-G-CSF mAb-treated WT mice had reduced disease severity, with markedly reduced neutrophil infiltrate, but little or no change in other myeloid inflammatory cells. In the absence of G-CSF, antigen-specific T cell responses remained intact in both disease models and IL-17A production was maintained.  We demonstrate that G-CSF controls ocular neutrophil infiltrate by modulating the expression of chemokine receptors - CXCR2 and CXCR4 - on peripheral blood neutrophils as well as CXCL2-mediated actin polymerization. These data establish an integral role for G-CSF-driven neutrophil responses in CNS autoimmunity, operating both within and outside the bone marrow and identify G-CSF as a potential therapeutic target in the treatment of human uveoretinitis and multiple sclerosis.