Pembrolizumab is an immunoglobulin G4 isotype antibody that targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes. It is used in the treatment of advanced non-small cell lung cancer (NSCLC). The safety and efficacy of immunotherapy for autoimmune disease are currently unknown;immune-related adverse events induced by immune checkpoint inhibitors (ICIs) have been reported. We report a case of severe colitis induced by the administration of pembrolizumab for pulmonary adenocarcinoma in a patient with ulcerative colitis. A 72-year-old man with a 3-year history of ulcerative colitis maintained clinical remission with mesalazine. The recurrence of lung adenocarcinoma was diagnosed and treated with pembrolizumab as second-line treatment. Diarrhea and bloody stool recurred 5 months after the first administration of pembrolizumab. The colitis did not respond to corticosteroids and infliximab. Because of the recurrence of ulcerative colitis, treatment of the lung adenocarcinoma was discontinued, and the patient died 1 year after the first administration of pembrolizumab. Few cases of severe colitis induced by the administration of pembrolizumab in patients with ulcerative colitis have been reported. This case suggests that the clinical stratification of autoimmune disease and typical standards of effectiveness of treatment are needed for patients with autoimmune disease who are treated with ICIs.