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AIM: To investigate if there are changes in serotonin(5-HT) levels, enterochromaffin (EC) cells and mast cells in small intestinal mucosa of patients with irritable bowel syndrome (IBS).METHODS: Diarrhea-predominant (IBS-D, n = 20), or constipation-predominant (IBS-C, n = 18) IBS patients and healthy controls (n=20) underwent colonoscopy and peroral small intestinal endoscopy, and mucosal samples were obtained at the descending part of the duodenum, proximal end of jejunum and terminal ileum. High-performance liquid chromatography electrochemistry and immunohistochemical methods were used to detect 5-HT content, EC cells and mast cells.RESULTS: (1) There were no differences in the number and distribution of EC cells between IBS patients and the normal group. (2) The mucosal 5-HT contents at the duodenum, jejunum and ileum in IBS-C patients were 182 ± 90, 122 ± 54, 61 ± 35 ng/mg protein,respectively, which were all lower than those in the normal group (256 ± 84, 188 ± 91, and 93 ± 45 ng/mg protein, respectively), with a significant difference at the jejunum (P＜0.05). There were no differences in the small intestinal mucosal 5-HT contents between IBS-D patients and the normal group. The mucosal 5-HT contents at the duodenum were significantly higher than those at the ileum in the three groups (P＜0.001). (3)The numbers of mast cells in patients with IBS-C and IBS-D at the ileum were 38.7 ± 9.4 and 35.8 ± 5.5/high power field (hpf), respectively, which were significantly more than that in the normal group (29.8 ± 4.4/hpf)(P ＜ 0.001). There was no significant difference in the numbers of mast cells at the other two parts between IBS patients and the normal group. The numbers of mast cells in IBS-C, IBS-D, and normal groups were all significantly higher at the ileum (38.7 ± 9.4, 35.8 ± 5.5,29.8 ± 4.4/hpf, respectively) than at the duodenum (19.6± 4.7, 18.5 ± 6.3, 19.2 ± 3.3/hpf, respectively, P ＜ 0.001).CONCLUSION: The changes in the 5-HT signaling pathway at the jejunum of IBS-C patients and the increase in mast cells in patients with IBS at the terminal ileum may offer evidence to explain the pathogenesis of IBS.