To explore a reliable rat model of IBS-D by comparing the differences of different psychological stress. Methods:A total of 40 neonatal rats were randomly divided into 2 groups:normal group and maternal separation group. The pups in the maternal separation group were exposed to 3 h period daily maternal separation from postnatal day 2～14, and then they were randomly divided into single maternal separation group(S) and combined stress group (SR) in the 9th week. The pups it the other group were left untreated and then were randomly divided into normal group (N) and chronic restraint stress group(R) in the 9th week. The group R and SR underwent chronic restraint stress by specially designed restraint frame 3 h daily for 3 weeks. The group N and S were left untreated. In the 12th week, the group N was given normal saline by gavage, the group R, S and SR were given Senna decoction (0.45 g/mL) by gavage(4.5 g/kg)for 7 days. The visceral sensitivity was tested and the animal behavior was evaluated by open field test before and after the chronic restraint stress. The fecal scores were calculated. The level of serum 5-HT, the number of mast cells (MC) and enterochromaffin cell (EC) of the proximal colon colon were tested after the modeling.Results:1) Visceral sensitivity:Before the restraint stress, the pain threshold of the maternal separation group(S、SR) were lower compared to the other group(N、R) (P<0.05). After the modeling, the pain threshold of the group S and SR were lower than group N (P<0.05), and there was no significant difference between the group R and N. 2) Fecal score:The fecal scores of group S, R, SR were significantly higher than the group N (P<0.05), the fecal score of group SR was significantly higher than the group S and R (P<0.05). 3) Open field test:Before the restraint stress, the horizontal motion of the group S and SR tend to decrease compared to the group N、R, while the vertical motion of the group S and SR were significantly lower compared to the group N、R(P<0.05). After the modeling, the horizontal and vertical motion of the group S and SR significantly decreased compared to group N (P<0.05). The horizontal motion of group SR was significantly decreased compared to the group S (P<0.05). 4) Serum 5-HT:The level of serum 5-HT increased in the group S and SR compared to the group N (P<0.05).There was no significant difference between the group R and N. And the level of serum 5-HT increased in the group SR compared to the group N (P<0.05). 5) Pathological features, the number of MC and EC in the proximal colon：There were no obvious abnormality in the Pathological features.The number of the MC in group SR increased significantly compared to the group N (P<0.05)，but there was no significant difference in the other groups. The number of EC in group R,S and SR increased significantly compared to group N (P<0.05).There were no significant difference among the group R, S and SR. Conclusion:The maternal separation stress, combined with chronic restraint stress and senna decoction by gavage could duplicate the IBS-D rat model, which is characterized with visceral hypersensitivity, abnormal defecation and depression.