Objective: Diffuse alveolar damage (DAD) is a pathological pattern of acute respiratory distress syndrome that can be a direct cause of death in many diseases. The process of fibrosis and myofibroblasts (MFS) in DAD were investigated. Methods: Lung tissues obtained at autopsy from 23 cases of DAD were studied with light microscopy and the light microscopic immunoperoxidase method. Results: Four cases of exudative stage DAD and 18 cases of organizing stage DAD were detected. All cases showed hyaline membranes and α smooth muscle actin-positive MFS. MFS were located in the alveolar walls in the exudative stage. MFS were observed in the intra-alveolar spaces in all 18 cases of the organizing stage. Fifteen of 18 cases showed Mib-1- positive proliferating MFS in the alveolar spaces. Eleven of 18 cases of the organizing stage showed proliferation of MFS in the alveolar walls themselves, in addition to that in the intra-alveolar spaces. Discussion: In previous reports, intra-alveolar fibrosis composed of MFS or fibroblasts or both was essential in lung fibrosis. In this study, we found that (1) in the early stage of DAD, MFS appear in the alveolar walls, (2) in organizing DAD, intra-alveolar fibroses were formed as in the previous reports, (3) in addition, fibroses were formed in the alveolar walls themselves in 11 of 18 cases of organizing DAD.