Recent studies indicate that early T lymphocyte activation 1 (Eta-1), also known as osteopontin, is a cytokine contributing to the development of Th1 immunity. In the present report, the role of Eta-1 in experimental autoimmune encephalomyelitis (EAE), a disease associated with Th1 immunity, was examined by analysis of disease progression in Eta-1-deficient (Eta-1−/−) mice. Although incidence and onset of peptide-induced EAE were found to be similar in Eta-1−/− and Eta-1+/+ mice, Eta-1−/− mice displayed significantly lower mean maximal clinical score and faster recovery without spontaneous relapses. Accordingly, decreased inflammatory infiltration and demyelination were observed in the spinal cords of Eta-1−/− mice. Furthermore, in comparison to Eta-1+/+, Eta-1−/− CD4+ T cells had reduced expression of IFN-γ and TNF-α upon ex vivo restimulation. Taken together, these results suggest that Eta-1 may sustain autoimmune responses by assisting in maintenance of Th1 immunity during EAE.