Polymeric immunoglobulin receptor (pIgR) plays an intrinsic role in protecting the intestinal tract from invading pathogens. In the present study, we observed a decrease in pIgR in colon lysate from mice with dextran sodium sulfate (DSS) colitis. A decrease in pIgR was detected in both mRNA and protein levels. Histologic examinations revealed marked destruction of intestinal epithelial cells (IECs), and only a small number of regenerating IECs expressed pIgR. These results suggest that the decrease in pIgR was due to the destruction of IECs. Because activation of toll-like receptor 3 slows the progression of DSS colitis, we injected polyriboinosinic: polyribocytidylic acid (poly I:C) intraperitoneally and observed the correlation between pIgR level and severity of DSS colitis. Poly I:C markedly decreased progression of DSS colitis, and pIgR levels significantly recovered. Furthermore, we found that expressions of IFN-γ and TNF-α were higher in DSS colitis. These results indicate that the decrease in pIgR was not compensated for by increased expression of these cytokines. In sum, our findings show that pIgR levels vary according to the severity of DSS colitis and that these changes might be useful as a biomarker of the severity of inflammatory bowel disease.