Programmed death ligand (PDL) is a new member of the B7 family of costimulatory molecules that specifically interacts with programmed death 1 (PD-1) expressed on activated T cells, B cells, and myeloid cells. Collagen II (CII)-induced arthritis (CIA) is an experimental model of arthritis that has been used to dissect the pathogenesis of human rheumatoid arthritis. In this study, we have investigated the effects of PDL-Ig on CIA. Administration of PDL-Ig significantly ameliorated the disease as assessed by clinical arthritis score and histology in the joints. Expression of proinflammatory cytokines, such as IL-17 and IL-23, in the serum was reduced by PDL-Ig treatment. These results showed a beneficial effect of PDL-Ig on CIA through anti-inflammatory actions and inhibition of cell proliferation in response to CII, suggesting that the PD-1-PDL pathway may be involved in the pathogenesis of CIA, and thus PDL-Ig may be a useful therapy for the improvement of human rheumatoid arthritis.