Background/Aims: Psychological factors and subtle histopathological changes have been implicated in irritable bowel syndrome (IBS). The aims of the present study were to investigate whether the numbers of enterochromaffin (EC) cells, mast cells, and lamina propria T lymphocytes are altered in IBS, and evaluate the relationship of such alterations with psychological factors. Methods: Forty-two consecutive IBS patients (M : F = 17:25, mean age 48 years) fulfilling the Rome III criteria and twelve asymptomatic healthy controls underwent rectal biopsy. Immunostaining was performed for EC cells, mast cells, and lamina propria T lymphocytes. Results: The IBS group included five post-infectious (PI) IBS and 37 non-PI IBS patients. Significantly more EC cells, mast cells and lamina propria T lymphocytes were observed in PI IBS patients. Mast cells significantly increased in non-PI IBS-D (diarrhea) patients, but not in non-PI IBS-C (constipation) and non-PI IBS-M (mixed) patients. Enterochromaffin cell numbers were not significantly altered in non-PI IBS patients. Anxiety and depression scores did not differ between IBS patients with and without abnormal increase in EC cell or mast cell counts, defined as more than the mean of controls + 2 standard deviations. Enterochromaffin cell, mast cell, or lamina propria T lymphocyte numbers were poorly correlated with anxiety and depression scores in the IBS group. Conclusions: Enterochromaffin cells, mast cells, and lamina propria T lymphocytes significantly increase in PI IBS, whereas only mast cells significantly increase in non-PI IBS-D. Such histopathological changes do not seem to be directly associated with psychological factors.