The recent development of effective and safe devices to remove leukocytes selectively from circulating blood has facilitated the application of leukocytapheresis for the treatment of inflammatory bowel disease (IBD). Successful results of preliminary trials of leukocytapheresis for IBD led to several nationwide multicenter clinical trials in Japan. As a result, five or six consecutive leukocytaphereses, which were undergone weekly, improved both symptoms and endoscopic findings in approximately 60%-80% of patients with ulcerative colitis (UC). In Japan, leukocytapheresis is now considered to be one of the standard treatments for UC patients with refractory disease to avoid surgery. Here, the current status of indications and mechanisms of action on UC are analyzed by reviewing the results of Japanese multicicenter trials, and the possible application for Crohn's disease is also discussed.