The role of coagulation-fibrinolysis system in experimental autoimmune encephalomyelitis (EAE) was studied by using batroxobin, derived from the venom of the South American pit viper Bothrops atrox moojeni. Batroxobin converts circulating fibrinogen into an insoluble form and causes a profound degree of afibrinogenemia. Batroxobin treatment (30 BU/kg/day) suppressed clinical signs of cell transferred EAE; the mean cumulative clinical score for batroxobin treated rats was 3.97, while saline treated controls scored 6.9 (P < 0.01). Plasma fibrinogen concentration decreased significantly in batroxobin-treated rats. Histologically, the degree of perivascular mononuclear cell infiltration in the spinal cord was not suppressed in batroxobin-treated rats compared to saline-treated control rats, however, deposition of fibrin around the vessels in the spinal cord was markedly suppressed in batroxobin-treated rats. These findings suggest that batroxobin suppresses EAE by preventing fibrin deposition, and provide evidence that CNS-associated deposition of fibrin and ensuing fibrinolysis, together with increased permeability of blood brain barrier (BBB), are related prerequisites for the clinical manifestation of EAE.