Background/Aims: Irritable bowel syndrome (IBS) is a common disease often considered as a functional intestinal disorder. Inflammation in IBS is a quite intriguing theory. The aim of this study was to investigate tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 expression in inflammatory bowel disease (IBD) patients, IBS patients and normal controls. Methods: IBS and IBD patients along with normal controls were recruited in the study. In all groups, 2 pinch biopsies were taken at each of 3 anatomical sites (terminal ileum, cecum, and rectum). IBS patients were also subcategorized according to the syndrome clinical manifestations. Two monoclonal antibodies (mAb), TNF-α mAb and IL-6 mAb, and one polyclonal antibody IL-1β mAb were applied for immunohistochemical analysis. Results: In IBD patients intensity of TNF-α and IL-1β were lower than in IBS patients or controls, while IL-6 was significantly increased comparing to the aforementioned groups. In IBS patients TNF-α was increased comparing to IBD patients or controls, while IL-6 and IL-1β were similar to controls. In IBS subgroups, TNF-α was lower in diarrhea predominant IBS patients and higher constipation predominant IBS patients. Differences among IBS subgroups regarding IL-6 and IL-1β were nonsignificant. Conclusions IL-6 seems to be the most important proinflammatory cytokine in IBD patients, while TNF-α could play a more significant role in IBS pathogenesis.