Ulcerative colitis (UC) is an inflammatory bowel disease, and inflammation is its important therapeutic target. A wide variety of medications have been used to treat UC, including 5-aminosalicylates (5-ASA), salazosulfapyridine, and anti-tumor necrosis factor (TNF)-α antibodies. However, some patients fail to respond to these treatments. Several clinical trials indicate that Qing Dai/Indigo Naturalis (QD) powder derived from plant extracts ameliorate ulcerative colitis. However, the therapeutic mechanism of QD is unclear. In this study, we investigated the effect of QD on inflammatory response in the distal colon of UC model mice. UC was induced by administration of 1.25% dextran sulfate sodium (DSS) to 6 week-old male C57BL/6J mice. QD was distinguishingly more effective than 5-aminosalicylate and salazosulfapyridine in suppressing weight loss, diarrhea, and rectal bleeding. DSS induced the expressions of inflammatory genes on day 6 of DSS administration, and QD inhibited these gene expressions. These observations suggest that QD interferes with the early events of inflammatory pathway.