Objective: To establish the diarrhea-predominant irritable bowel syndrome (IBS-D) mouse model by gavage of Senna folium combined with chronic restraint stress, and to determine the appropriate concentration of Senna folium. Method: According to the concentration of Senna folium used in literature with the IBS-D mouse model, the concentration gradient was established and the experiment was carried out. Female C57BL/6 mice were divided into the normal group (Group N), low dose group (0.25 g/mL Senna solution, Group L), medium dose group (0.50 g/mL Senna solution, Group M), and high dose group (1.0 g/mL Senna solution, Group H) with 10 mice in each group. After 14 days, the defecation, the diarrhea index, the visceral sensitivity, and the morphological changes of colonic tissue in each group were observed and recorded, to compare the difference of different concentration models of Senna folium. Result: Compared with Group N(42.9%±12%), Group L(80.3%±5.8%), Group M(80.5%±3.4%), and Group H(81.9%±2.7%) had significantly higher 6-h fecal water content (P < 0.01). Compared with Group N (0.00±0.00), the diarrhea index of mice in Group L(0.57±0.16), Group M(0.62±0.23) and Group H(0.60, 0.23) also increased significantly(P < 0.01). Compared with Group N(0.65(0.60, 0.65)), Group M(0.32(0.24, 0.39)) and Group H(0.34(0.27, 0.47)) had significantly lower minimum visceral pain threshold and higher visceral sensitivity (P < 0.05) . In addition, the first blue stool time in Group M(98.15(93.41,100.44) min) was significantly shorter than that in Group N (186.81(109.28.192.05) min) (P < 0.01), and the total number of stools in Group M (22.4±3.73) was also significantly higher than that in Group N (17.90±4.48) (P < 0.05). Conclusion: Compared with 0.25 g/mL and 1.0 g/mL, 0.50 g/mL Senna intragastric administration combined with chronic restraint stress could better simulate the clinical symptoms of IBS-D.