We describe a 31-year-old patient with ulcerative colitis who was successfully treated with prednisolone (PSL). Immunologic analyses were performed during the treatment course. Suppressed natural killer (NK) cell activity and increased levels of the CD4/CD8 ratio were observed on admission. Transient restoration of NK cell activity was obtained by PSL treatment. However, it returned to the initial low level in spite of the improvement of clinical symptoms. Possible mechanisms are discussed for involvement of the immune system in the pathogenesis of ulcerative colitis (UC).