Hypertension promotes and escalates kidney injury, including kidney fibrosis. Fractalkine/CX3CL1 is a unique chemokine that works as a leukocyte chemoattractant and an adhesion molecule. Recently, fractalkine/CX3CL1 has been reported to promote tissue fibrosis via its cognate receptor, CX3CR1. However, the involvement of the fractalkine-CX3CR1 axis in the pathogenesis of hypertensive kidney fibrosis remains unclear. The impacts of the fractalkine-CX3CR1 axis on hypertensive kidney fibrosis were investigated in a deoxycorticosterone acetate (DOCA)-salt hypertensive model in CX3CR1-deficient mice, which were sacrificed on day 28. The blood pressure levels were similarly elevated in both CX3CR1−/− C57BL/6 and wild-type C57BL/6 mice. Fractalkine and CX3CR1 were upregulated in kidneys that were damaged by hypertension. Deficiency in CX3CR1 inhibited kidney fibrosis, as evidenced by a decrease in the presence of interstitial fibrotic area detected by type I collagen in Mallory–Azan staining, concomitant with the downregulation of transforming growth factor (TGF)-β 1 and type I procollagen mRNA expression in damaged kidneys. The CX3CR1 blockade also decreased the number of infiltrating F4/80-positive macrophages in damaged kidneys. These results suggest that the fractalkine-CX3CR1 axis contributes to kidney fibrosis in a hypertensive mouse model, possibly by the upregulation of macrophage infiltration and the expression of TGF-β 1 and type I collagen.