The purpose of this study was to investigate the expression of interleukin (IL)-21 in rats with inflammatory bowel disease (IBD). Fifty adult Wistar rats were randomly divided into two groups: DSS, in which IBD was induced by giving the rats 7% DSS for seven days in their water, and a water control. Blood samples were collected and the concentration of IL-21 in serum was detected by enzyme-linked immunosorbent assay. Colon tissue of rats was examined by immunohistochemical staining. Rats in the DSS group were lethargic, with matte coat color and decreasing body weight. In the DSS group, brown loss stool appeared after four days, and blood appeared in the stool along with dark red hematocele in the intestinal cavity after ten days. Rats in the control group were active and body weight increased regularly. Their stool was black and granular and the color of the intestinal canal was pink. The original body weight of all rats in both groups was similar but seven days after induction of IBD, the weight of the DSS rats dropped significantly compared to the control group (P < 0.05). Serum IL-21 levels were 1.37 +/- 0.43 pg/mL in the control group and 3.86 +/- 1.27 pg/mL in the DSS group (P < 0.05). More IL-21 positive cells were detected in the intestinal mucosal epithelial cell layer and the lamina propria of the submucosa in the DSS group than in the control group. In conclusion, IL-21 is involved in the pathological process of IBD.