Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is expressed on the membrane of leukocytes and vascular endothelial cells. PECAM-1 has been shown to play an important role in the process of leukocyte transmigration in various animal models of acute inflammation. We investigated the role of PECAM-1 in the progression of arthritis by systemically administering anti-murine PECAM-1 monoclonal antibody, 2H8, to DBA/1J mice with collagen-induced arthritis (CIA). Subcutaneous administration of dexamethasone (0.5 mg/kg per 2 days) significantly reduced hindpaw swelling and the clinical score of established CIA. Intraperitoneal administration of 2H8 (0.25 mg/mouse per 2 days) significantly inhibited hindpaw swelling in a time-dependent manner. 2H8 also significantly prevented further deterioration in the clinical score, but failed to reverse joint destruction discernible at the histological level. Both dexamethasone and 2H8 inhibited body weight decrease by preventing the further development of arthritis. Histopathological assessment revealed that 2H8, as well as dexamethasone, inhibited inflammatory cell transmigration into the synovium of the hind paw joint and ameliorated synovitis and cartilage erosion. These results suggest that PECAM-1 plays an important role in the progression of CIA and that an inhibitor of PECAM-1 might have therapeutic value for clinical treatment of rheumatoid arthritis.