SODs, and more particularly Cu/Zn-SOD, have attracted considerable attention as potential drugs for the treatment of IPF. This is because, of the three types of human SODs (Cu/Zn-SOD, mitochondrial manganese-SOD, and extracellular-SOD), Cu/Zn-SOD accounts for 80% of SOD activity within the lung.33 However, the low stability of Cu/Zn-SOD in plasma and low affinity for tissue is an obstacle for its clinical use. PC-SOD, a derivative of SOD with higher stability in plasma and higher tissue affinity, offers an attractive alternative to Cu/Zn-SOD. In a phase 1 clinical study, IV administered PC-SOD (40-160 mg) had a terminal half-life of > 24 h, with good safety and tolerability.34,35 A phase 2 clinical study showed that IV administered PC-SOD (40 or 80 mg) significantly improved the symptoms of not only patients with ulcerative colitis36 but also patients with IPF (Kamio K, Azuma A, Ohta K, et al, unpublished results, October 12, 2011). However, when considering the quality of life of patients, the present clinical protocol of PC-SOD administration based on daily IV infusion for 4 weeks needs to be improved. Given our recent finding that inhaled PC-SOD is effective against pulmonary fibrosis in mice,22 we believe that inhalation of PC-SOD may provide a viable option for the treatment of patients with IPF. In this study, we performed a series of experiments to investigate the efficacy of this approach in an animal model.