BACKGROUND: Inflammatory T cells including Th17 cells play a pivotal role in the pathogenesis of EAE. As all-trans retinoic acid inhibits development of Th17 cells. We examined the effect of Am80, a synthetic RAR-agonist with superior pharmacological properties, on EAE. METHODS & RESULTS: During the course of anti-CD3 stimulation of splenic T cells in the presence of IL-6 and TGF-β, Am80 exerted strong suppression of Th17 differentiation and reciprocal induction of Foxp3+ T cells. Am80 successfully suppressed IL-17 secretion and RORγt expression from already differentiated Th17 cells as well. Oral administration of Am80 ameliorated severity of MOG-induced EAE in B6 mice along with a reduced production of inflammatory cytokines and RORγt expression by CNS-infiltrating T cells. Am80 suppressed antigen-specific IL-17 production by draining lymph node cells of MOG-immunized mice. Therapeutic treatment with Am80 from day 13 after immunization was also effective for amelioration of EAE. CONCLUSION: Synthetic retinoid Am80 successfully inhibits inflammatory cytokine production by pathogenic T cells in EAE and could provide a novel therapeutic approach for multiple sclerosis.