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Abstract Expansion and commercialization of nanotechnology mean that it is important to understand the potential health hazards of manufactured nanoparticles. Here, we focused on the effect of fullerene, a type of nanoparticle already in commercial use, on delayed-type hypersensitivity (DTH) induced by methyl-bovine serum albumin (mBSA). Delayed-type hypersensitivity was induced with methyl-bovine serum albumin in female C57BL/6 mice. A colloidal suspension of crystalline C60 (nano-C60 ; average particle size 165 nm; 200 μL; 5.5 μg/mL) was injected intravenously twice, just before immunization and challenge with mBSA. Nano-C60 treatment significantly attenuated footpad swelling, compared with that in DTH-disease control mice. Cytokine analysis indicated that nano-C60 treatment switched the cytokine balance towards Th1-dominance. Pro-inflammatory cytokines IL-6 and IL-17 were significantly increased in DTH mice, and these increases were significantly suppressed by nano-C60 treatment. Suppression of IL-17 by nano-C60 was confirmed in an in vitro splenocyte culture. However, production of TNF-α was increased in DTH mice, and the increase was significantly enhanced by nano-C60 treatment. The ratio of regulatory T (Treg) cells to total T (CD4+ ) cells was also significantly increased by nano-C60 treatment, compared with that in DTH-disease control mice. Nano-C60 treatment showed significant immunomodulatory effects in a mouse DTH model: IL-6 and IL-17 production was down-regulated, and the Treg cell ratio was up-regulated, concomitantly with attenuation of the pathology of DTH.