Desquamative interstitial pneumonia (DIP) is a rare interstitial pneumonia often caused by smoking. DIP is typically regarded as a chronic disease, but acute DIP exacerbations can occur, and some have resulted in death. Factors that can provoke a DIP exacerbation are not well described in the literature. We present a case of a 58-year-old male with DIP, who after being treated successfully with smoking cessation and steroids for 7 months, required hospitalization for acute hypoxemic respiratory failure. This acute episode was very likely an exacerbation of his DIP after a smoking relapse period of 6 weeks prior to this acute presentation. This report also highlights unique CT findings in a DIP case of pleural effusions and mediastinal adenopathies seen chronically and relapsing acutely. To the best of our knowledge, CT findings of pleural effusions and mediastinal adenopathies concurrently have not been described in a case of DIP in chronic or acute conditions.