Indoleamine 2,3-dioxygenase (IDO) exerts immunomodulatory effects due to enzymatic activities catalyzing the essential amino acid L-tryptophan. IDO activity might play an important role in regulating immune responses exerted by antigen-presenting cells as a potent tool to help escape from assault by the immune system. In this study, we performed immunohistochemical analysis for IDO expression using mouse anti-human IDO monoclonal antibody in 119 tissue samples of diffuse large B-cell lymphoma (DLBCL) obtained before treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Not only the lymphoma cells themselves but also dendritic cells (DCs) expressed IDO. Positive IDO expression in lymphoma cells was found in 38 cases (32%). Complete remission rates in patients with IDO-positive DLBCL and IDO-negative DLBCL were 55.3% and 79.0% (p=0.008), while 3-year overall survival rates were 49.8% and 78.8%, respectively (p=0.0003). IDO activity might thus play an important role in DLBCL and cells that express IDO appear important for determining outcomes after R-CHOP treatment. IDO might represent a candidate therapeutic target for DLBCL patients who show resistance to chemotherapy.