Ulcerative colitis (UC) is a chronic inflammatory bowel disease of the colorectum, with mucosal infiltration by activated leukocytes, which are the result of complex interactions between lymphocytes, antigen, and dendritic cells (DCs). We carried out lymphocyto-plasmapheresis (LCPA) in a UC patient with the aim of removing lymphocytes, DCs and inflammatory cytokines (ICKs). A 42-year-old female with UC in moderate activity phase was submitted to 5 weekly LCPA treatments. Before and after LCPA we monitored: (i) the percentage of T, B, NK lymphocytes, monocytes, and peripheral blood lymphoid and myeloid DCs; (ii) the T lymphocyte subpopulations; (iii) the ICKs; and (iv) the immune complexes (IC). We achieved the interruption of all pharmacological therapies, and so far the clinical and histological remission has lasted for 24 months. The flow cytometric assessment of the leukocyte subpopulations did not show any relevant variation of their numbers after LCPA, while TNFα, IL-6, IL-12 and serum IgG-C1q ICs decreased. In the present case, the contemporary depletion of plasma, lymphocytes and DCs, allowed LCPA to emerge as an efficient alternative to UC pharmacological therapy without affecting the number of white blood cells, DCs and leukocyte subpopulations that were assessed. Further studies are needed both to address LCPA mechanism of action and optimal apheresis protocol, and to compare this form of therapy to a placebo control group.