We studied the effects of 0.25% indomethacin (IM) spray as an in-hospital preparation on the pain of stomatitis after hematopoietic stem cell transplantation in 9 patients with various types of leukemia by measuring the change in pain and the decrease in morphine dose. Stomatitis above grade 2 (painful erythema, edema, or ulcers but can eat or swallow) appeared in all patients as white blood cell (WBC) counts declined after transplantation, and clockwise hysteresis was observed between WBC counts and the grade of stomatitis. When the patients used IM spray for the pain of stomatitis and were judged the grade of pain using a face scale of five grades (0-4) before and after the use of this spray, the mean grades of pain at the maximal pain during the appearance of stomatitis declined from 3.4 to 1.8 (n = 5). Furthermore, the concurrent intravenous dose of morphine markedly decreased during IM spray use. There was no complaint concerning the taste and convenience of IM spray by patients. The risk of systemic adverse effects was considered relatively low based on the small amounts of IM applied to the mouth mucosa. In conclusion, it is suggested that IM spray is effective for the relief of stomatitis pain in patients who have undergone hematopoietic stem cell transplantation and is a useful preparation for immediate self-medication upon the appearance of stomatitis pain. We considered that the application of IM spray will contribute to the improvement of patient quality of life.