Abstract: Objective This study sought to establish a diarrhea-predominant irritable bowel syndrome (IBSD) mouse model by gavage different mass concentrations sennae folium combined with chronic restraint stress, and to determine the appropriate mass concentration of sennae folium to establish IBS-D mouse model. Methods The mass concentration of sennae folium used for the IBS-D mouse model followed suggested amounts in the literature and on that basis, the mass concentration gradient was established prior to conducting the experiment. Female C57BL/6 mice were divided into a normal group (Group N), a low-dose group (Group L; 0.25 g/mL sennae solution), a medium dose group (Group M; 0.50 g/mL sennae solution), and a high-dose group (Group H; 1.0 g/mL sennae solution), with 10 mice per group. After 14 days, the defecation, diarrhea index, visceral sensitivity, and morphological changes in the colonic tissue in each group were observed and recorded to compare the differences among models established with varying mass concentrations of sennae folium. Results Compared with Group N (42.90 ± 11.90)%, Group L (80.30 ± 5.77)%, Group M (80.50 ± 3.44)%, and Group H (81.90 ± 2.68)% 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 visceral pain threshold and higher visceral sensitivity (P<0.01). Additionally, 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 significantly higher than that in Group N (17.90 ± 4.48) (P<0.05). Conclusions Compared with 0.25 and 1.0 g/mL, 0.50 g/mL sennae folium gavage, combined with chronic restraint stress, can better simulate the clinical symptoms of IBS-D.