Objective Based on the observation of the changes of symptoms, histopathology, visceral sensitivity, mast cell activation, autophagy, and Beclin-1 and Claudin-2 expression in rats, we established and evaluated a new rat model of diarrhea-predominant irritable bowel syndrome (D-IBS) induced by restraint-stress combined with capsaicin (CAP) administration. Methods Forty healthy 5-week old male Sprague Dawley (SD) rats were randomly divided into normal group, model group I, model group Ⅱ and model group Ⅲ, with 10 rats in each group. The D-IBS model was established by restraint-stress combined with intragastric administration of CAP (2 mL/100 g body weight, 0.125% in group I, 0.250% in group Ⅱ, 0.500% in group Ⅲ), tail clipping and forelimb restriction for 30 minutes every day for 2 weeks. The rats in the control group were treated with saline for 2 weeks. The number of contraction of abdominal wall and arched back were measured by Power Lab instrument. The mast cell activation was detected using aldehyde-magenta-orange G staining. Light and electron microscopic examinations were performed to detect the morphology and autophagy of colonic tissues. The expressions of Beclin-1 and Claudin-2 in the colonic mucosa were detected by streptavidin-biotin complex (SABC) immunohistochemical staining. Results All rats in the model group Ⅲ died during the experiment. Compared with the control group and model group I, the stool frequency was increased and the visceral sensitivity threshold decreased in the model group Ⅱ, and there were statistically significant differences between the model group Ⅱ and the control and model groups I (P< 0.05). The colonic mucosa, mucosal epithelium and glands in each group showed normal morphology and there was no submucosal vasodilatation and diffuse inflammatory cell infiltration. Except for the control group, round purple-reddish staining spots were observed in the rat mucosal stroma or submucosa in the model groups I and Ⅱ, indicating an increased expression of mast cells. The autophagy, expressions of Beclin-1 and Claudin-2 in the colonic epithelium were significantly increased in the model group Ⅱ compared with control group and model group I (P< 0.05). Conclusions The model of D-IBS induced by restraint-stress combined with capsaicin is characterized by increased diarrhea, visceral hypersensitivity, increased mast cell expression and autophagy of intestinal epithelial cells, and disruption of the intestinal mucosal barrier. This model is simple to set up and shows similar symptoms of human irritable bowel syndrome. Therefore, it is worthy of popularization and application.