Background: The pathophysiologic mechanisms underlying acute exacerbation of idiopathic pulmonary fibrosis (IPF) are not fully understood. Few studies have examined autopsy findings in patients who have died from an acute exacerbation of IPF. The pathologic findings in systemic organs have not been described. Methods: We retrospectively reviewed the autopsy findings in 12 patients who had died from an acute exacerbation of IPF and two of connective tissue disease-associated interstitial lung disease between 2005 and 2015. We recorded demographic and clinical characteristics, autopsy findings and cytologic findings in peripheral blood. Results: The median age at autopsy was 68 years (range 45-87 years); 11 subjects (78.5 %) were men. High-dose corticosteroid, cyclophosphamide and oxygen therapy had been administered to all patients. Underlying lesions had the usual interstitial pneumonia pattern; diffuse alveolar damage and contraction band necrosis were observed in all cases. Large cells expressing scavenger receptor A (SRA(+)) had been observed in the systemic circulation of 11 of the 14 cases (78.6 %) before acute exacerbation, and cells expressing tumor necrosis factor-alpha (TNF-alpha(+)) were detected after its diagnosis in nine (64.3 %). Both were detected in all cases at autopsy. There was neutrophil and platelet accumulation predominantly in capillaries, and extensive capillary endothelial cells injury. Conclusions: Our findings suggest that acute exacerbation of IPF has systemic consequences with multiple organ injury, with SRA(+) and TNF-alpha(+) cells in the systemic circulation playing central roles in multiple organ injury.