A 78 year old Japanese woman was transferred to our hospital for the treatment of a fracture of the left femoral neck in April, 2010. She had been taking oral corticosteroid (prednisolone 5 mg/day) for the treatment of idiopathic interstitial pneumonia since 2003, and had been treated by home oxygen therapy since 2007. She fell in the restroom at home and hurt herself, and was transferred to our hospital for treatment of a left femoral neck fracture in April, 2010. Her respiratory status was stable just after the transfer; however, she was transferred to the intensive care unit and started to receive mechanical ventilation due to rapidly progressive respiratory failure on the fourth day after admission. Chest X-ray and computed tomography revealed rapid progression of bilateral ground-glass attenuations, and acute exacerbation of interstitial pneumonia was clinically suspected. However, the elevation of D-dimer over time and characteristic findings of petechial hemorrhagic lesions on her palpebral conjunctivae and neck with microscopic findings of phagocytized lipid in alveolar macrophages in her endobronchial secretion led to the diagnosis of fat embolism syndrome. She was successfully treated with high-dose corticosteroid and sivelestat sodium, and she was discharged on the 21st day after admission. Although a differential diagnosis of acute exacerbation of interstitial pneumonia and fat embolism syndrome was necessary and difficult in the present case, characteristic findings of petechial hemorrhagic lesions of skin, palpebral conjunctiva and lipid-laden alveolar macrophages in endotracheal aspirate were useful for the accurate and prompt diagnosis of fat embolism syndrome.