Ulcerative colitis (UC) is a disease of acute on chronic at the active stage when lymphocytes, plasma cells as well as neutrophils and eosinophils infiltrate in the colonic mucosa. Molecular pathoimmunology of UC was discussed in this article from the viewpoint of disease susceptibility gene, immune activation gene of immunocompetent cells, molecular biology of cytokines, and molecular biology of colonic epithelial cells. HLA-DR2, DRB1* 1502, is the most susceptive gene for development and intractability of Japanese UC, and HLA-BW52 which was most frequently associated with Japanese UC and HLA-B35 which was also associated with Jewish UC were reported to have a common origin. Expression of IL-2 receptor and HLA-DR protein used as immune activation genes of lymphocytes was accelerated in UC. Overexpression of proinflammatory cytokines such as IL-1, IL-6 and IL-8 was found in the colonic mononuclear cells of UC, but IL-2 mRNA expression was not accelerated in UC. Therefore, immunological imbalance in the colonic mucosa may play an important role in the pathophysiology of UC.