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CCL20 expression is known to increase in the mucosal tissues of inflammatory bowel diseases (IBDs). Moreover, the discovery of Nod2 as the IBD1 susceptibility gene has underscored the significance of blood mononuclear cells in IBD pathogenesis. Methods: This study addresses whether CCL20 expression is similarly altered in peripheral blood mononuclear cells (PBMCs) of patients with ulcerative colitis (UC), a major type of IBD in Korea. Results: Expression of CCL20 was significantly up-regulated in the PBMCs of patients with UC compared with those of normal healthy controls. Interestingly, untreated UC groups expressed higher levels of CCL20 mRNA than either treated UC or normal control groups, suggesting that CCL20 could be modulated by anti-inflammatory drugs. Accordingly, a strong association between CCL20 levels and disease activity index was observed. Supporting these findings, results from a 3-month follow-up study revealed that the UC groups treated with 5-aminosalicylic acid and glucocorticoid exhibited dramatic decreases of CCL20 mRNA in PBMCs, accompanied by ameliorated disease states. Moreover, tumor necrosis factor-α− or interleukin-1β-induced CCL20 secretion was greatly diminished by 5-aminosalicylic acid and/or glucocorticoid treatment of human intestinal epithelial HT-29 cells. Of note, CCR6+ cell populations were significantly reduced in the blood of severe patients with UC compared with normal controls, whereas no significant changes in CCR6+ cell populations were observed in the blood of patients with mild UC or acute colitis. Conclusions: Collectively, these findings suggest that CCL20 expression in blood mononuclear cells is associated with altered immune and inflammatory responses in patients with UC.