Formation of massive hematoma in the cavity of chronic pyothorax (CP) has been described previously, but its mechanism remained unclear. In the present study of 99 cases, the vascular lesions in the wall of CP were examined by histological methods, including immunohistochemistry. The age of patients ranged from 42 to 80 years (mean 57 years), with a male to female ratio of 3.3. Histologically the CP wall was covered by a fibrin layer containing cellular debris and red blood cells. Directly beneath the fibrin layer, a fibrous layer of varied thickness was present that extended to the subserosal tissue or so-called fat plane defined by computed tomography. At the junctional region between the fibrin and fibrous layer, angiomatous lesions were observed in 33 cases (Group I). In the fibrin layer of this group, dilated vessels frequently bulged into the pleural cavity. In another two cases, closely packed large vessels with irregularly thickened walls resembled an arteriovenous fistula (Group II). In seven patients, histologic specimens showed a total necrosis. The remaining 57 cases without the findings in Groups I and II were categorized as Group III. These findings suggested that formation of angiomatous lesion preceed intrapleural bleeding, which occasionally progressed to form a massive hematoma.