Corticosteroid therapy may not be enough to control pneumonitis in some cases of severe drug-induced lung injury (DLI); however, an advanced treatment strategy for such cases is lacking. Here, we report the case of an 88-year-old man who presented with severe DLI, caused by Sai-rei-to. The patient visited our hospital complaining of progressive dyspnea. High-resolution computed tomography of the chest demonstrated bilateral patchy ground-glass opacities and infiltrative shadows. Nasal high-flow oxygen therapy was initiated because of severe hypoxemia. Bronchoalveolar lavage on admission revealed diffuse alveolar hemorrhage. Further, as the patient had started taking Sai-rei-to a month earlier, DLI caused by Sai-rei-to was the most likely diagnosis. Therefore, Sai-rei-to was stopped and steroid pulse therapy was initiated. However, he still required high-flow oxygen therapy. We considered an alternative diagnosis of Goodpasture syndrome or anti-neutrophil cytoplasmic antibody (ANCA) related vasculitis. We initiated the administration of cyclosporin A and therapeutic plasma exchange (TPE), but his respiratory condition did not improve satisfactorily. Therefore, we also initiated intravenous immunoglobulin (IVIG) therapy for the treatment of potential vasculitis. Subsequently, his respiratory status began to improve. Further, tests for anti-glomerular basement membrane antibody, myeloperoxidase-ANCA, and proteinase 3-ANCA revealed negative results. Drug-induced lymphocyte stimulation test performed six months after withdrawing methylprednisolone was positive for Sai-rei-to. Thus, the final diagnosis was DLI due to Sai-rei-to. Our findings demonstrate that in cases of severe acute respiratory failure due to DLI, the multi-modal therapy with plasma exchange and IVIG in addition to conventional treatment with prednisolone and immunosuppressant may be beneficial.