The aim of the present study was to investigate effects of low dose capsaicin (CAP) on substance P (SP) expression and histomorphometric properties of duodenum. In this study, 21-day-old rats were divided into three groups as control, CAP-treated and vehicle. The control group remained without any treatment. 0.5 mg/kg CAP prepared in a solvent and injected subcutaneously to CAP-treated group and vehicle group was injected with only solvent for 20 days. All rats were weighed daily. At the end of the experiment, tissue samples were collected and Crossman's triple staining was used for histomorphometric examinations and labelled streptavidin-biotin immunohistochemical technique was used for SP expression. The body weight gain was lower in the CAP treated group but no significant differences between the groups. Low dose CAP did not alter the depth of crypt in the duodenum but the height of the villus was higher than the other group (p<0.05). In the CAP treated group, SP immunoreaction was stronger than the other groups in the surface epithelium, Lieberkuhn crypts, in the Brunner's glands, smooth muscles layer, and the neurons of the myenteric plexus of the duodenum. Finally, low dose CAP, markedly stimulated expression of SP and also induced positively histomorphometric changes in the duodenum. As a result of low dose CAP treatment may play important role in epithelial cell functions and in the regulation of digestive system physiology.