Inflammatory bowel disease (ulcerative colitis and Crohn's disease) is a remitting and relapsing disease that affects millions of people worldwide. In the intestine, homeostasis between repair and signaling of the proinflammatory of the immune system is needful for the upkeep of intestinal balance. The recent evidence has highlighted the dysfunction of the immune system, particularly toll-like receptors (TLRs)-mediated immune system dysfunction, in the ulcerative colitis pathogenesis. The main objective of the current study was to analyze the expression level of TLR5 at the mRNA in ulcerative colitis patients and investigate the impacts of the TLR5 gene as genetic factors that contribute to the development of ulcerative colitis. The paraffin-embedded blocks were retrospectively collected from 25 patients diagnosed with ulcerative colitis and 25 cases with normal colonic tissue. The quantitative real-time polymerase chain reaction method was employed for the estimation of TLR5at the mRNA level. The analysis of the data of TLR5 gene expression revealed that the expression of this gene is downregulated in ulcerative colitis cases, as compared to that in normal colonic tissue. As evidenced by the results of this study, TLR5 may play a role in the development of ulcerative colitis; therefore, it should be introduced in the management of ulcerative colitis.