Acute respiratory distress syndrome (ARDS) is characterized by diffuse inflammation in the lung and resultant permeability edema. Polymyxin B-immobilized fiber (PMX-F) hemoperfusion is effective for sepsis-induced ARDS. High mobility group box-1 protein (HMGB1) is newly recognized as a proinflammatory cytokine. The aim of the study was to determine whether blood HMGB1 levels are increased in patients with ARDS and whether PMX-F treatment affects these levels. Subjects were 20 sepsis-induced patients with ARDS treated by PMX-F column and 20 age-matched healthy volunteers. Polymyxin B-immobilized fiber treatment was carried out twice at a rate of 100 ml/min for 2 hours. Systolic and diastolic blood pressures, the PaO2/FiO2 (PF) ratio and endotoxin, HMGB1, and urinary 8-hydroxy-2'-deoxyguanosine (OHdG) levels were measured before and after PMX-F treatment. Blood endotoxin levels, blood HMGB1 levels, and urinary 8-OHdG levels were significantly higher in patients with ARDS than in healthy volunteers. Systolic and diastolic blood pressures and the PF ratio increased significantly after PMX-F treatments. Polymyxin B-immobilized fiber treatment reduced blood endotoxin, blood HMGB1, and urinary 8-OHdG levels significantly. These data suggest that HMGB1 and oxidative stress play a role in the pathogenesis of ARDS and that PMX-F treatment may ameliorate increased blood HMGB1 and urinary 8-OHdG levels in patients with ARDS.