Abstract.Complementary DNA microarray technology allows the simultaneous analysis of the expression of hundreds to thousands of genes. We applied this technique to clarify the molecular mechanisms underlying the therapeutic effects of leukocytapheresis (LCAP) therapy in patients with ulcerative colitis (UC). A 776-gene microarray analysis was performed using whole blood cells from six normal subjects and six patients with active UC who had undergone filtration LCAP. Widespread gene upregulation was observed in patients with UC, compared with normal subjects. After LCAP, genes with proinflammatory actions, such as CD97, CD74, human leukocyte antigen-DRÎČ1 and -DP light chain, were downregulated, while genes responsible for antimicrobial actions, such as neutrophil gelatinase-associated lipocalin, and acute phase reactions, such as haptoglobin α1S and α1-acid glycoprotein, were upregulated. In conclusion, we identified several genes expressed in the whole blood cells of UC patients as well as the transcriptional events following LCAP. Following LCAP, the gene profile shifted toward a pattern indicating disease improvement. These results suggest a basis for the molecular mechanisms leading to the therapeutic effects of LCAP and also indicate new therapeutic targets, providing important prognostic information.