Purpose: This study examined the role of the monocyte chemokine receptor, CX3CR1, in experimental autoimmune uveoretinitis (EAU). Methods: EAU was induced in naive WT, Cx3cr1gfp/+ and Cx3cr1gfp/gfp C57Bl/6 mice or chimeric mice. Ocular disease severity was graded by histological analysis of resin sections. In addition, immunohistochemistry and confocal microscopy was performed on retinal wholemounts to characterize the monocytic infiltrate and changes in retinal microglia. To determine the relative roles of resident and blood-borne monocyte-derived cells in the active phase of uveoretinitis, EAU was induced 4 weeks post-transplant in chimeric mice (Cx3cr1gfp/gfp -> WT and Cx3cr1gfp/+ -> WT) and analysis performed at days 14, 16, 21 and 28 post-immunization. Results: Following EAU induction disease scores were not significantly different in WT, Cx3cr1gfp/+ and Cx3cr1gfp/gfp mice. Chimeric studies revealed both donor and host-derived monocyte-derived cells in the inner retinal layers during early EAU however it was donor monocytic cells that infiltrated the photoreceptors, the site of the target antigen. The absence of CX3CR1 did not impede the ability of monocyte-derived cells from Cx3cr1gfp/gfp donor mice to infiltrate during the peak of EAU. Conclusions: The lack of CX3CR1 on monocyte-derived cells does not significantly influence the onset or severity of EAU. In addition, chimeric studies revealed that it is primarily blood-derived monocytes that mediate photoreceptor damage in the effector phase of EAU and this process is not CX3CR1 dependent.