<i>Background/Aim:</i> Recent reports suggest that polymyxin B (PMX)-immobilized fiber may have beneficial effects in idiopathic pulmonary fibrosis (IPF) with acute exacerbation (AE). High mobility group box-1 (HMGB-1) is an important pro-inflammatory mediator that contributes to acute lung inflammation. This study was aimed to investigate whether PMX treatment affects serum HMGB-1 levels and oxygenation in IPF patients with AE. <i>Materials and Methods:</i> Twenty IPF patients with AE were treated by PMX. PMX treatment was carried out once daily for 2 successive days. Serum HMGB-1 levels were measured before and after PMX treatment. We also monitored arterial oxygen tension (PaO₂)/inspiratory oxygen fraction (FiO₂) (P/F) ratio. PMX fiber columns were analyzed to examine whether HMGB-1 was absorbed by PMX. <i>Results:</i> PMX treatment significantly improved both the serum HMGB-1 level and P/F ratio. HMGB-1 was detected in washing medium from the PMX column. <i>Conclusion:</i> PMX treatment may reduce serum HMGB-1 and improve oxygenation in patients with IPF with AE.