A 53-year-old man in whom reticulonodular shadows had been noted since 1999 in chest radiographs was admitted to our hospital in January 2003 with a complaint of persistent cough. His thoracic computed tomography (CT) showed diffuse ground-glass opacities in both lung fields and bilateral hilar and mediastinal lymphadenopathy. Histopathological findings from video-assisted thoracoscopic surgical biopsy included diffuse, monotonous interstitial pneumonia with accumulation of macrophages in the alveolar spaces and many lymphoid follicles, which was compatible with desquamative interstitial pneumonia (DIP). There was follicular hyperplasia in the enlarged lymph node without a suggestion of granulomous disease. He responded well to corticosteroid administration, resulting in an improvement of his clinical condition associated with a decrease in the ground-glass opacities. The bilateral hilar and mediastinal lymphadenopathy was slightly reduced. Since we could find no literature reporting DIP with bilateral hilar and mediastinal lymphadenopathy on thoracic CT, we consider the diagnostic problems and therapeutic response of this case to warrant a brief report.