Objective To observe the effects of chronic heterotypic intermittent stress ( HIS ) on the gastrointestinal immune system, particularly in terms of (1) the morphology of the gastric and colonic mucosa, and (2) intestinal microbial diversity. Methods We randomly divided 24 SD rats into a control group and a model group. The rats in the model group received HIS for 9 days. After the 9 days of modeling, five rats in the control and model group were randomly selected, and fecal samples were collected for gut microbial diversity analysis. Four of the 12 rats from each of the two groups were randomly selected for perfusion and fixation, and tissues from the gastric antrum and colon were taken for morphological observation. Plasma and adrenal tissues were taken from the remaining eight rats for assessment of corticosterone content. Results (1) After 9 days of HIS, the rats in the model group had gained significantly less weight than those in the control group (P= 0. 001). Furthermore, the corticosterone content in adrenal tissue was significantly lower in the model group vs. the control group (P= 0. 006), and the corticosterone content in plasma was higher in the model group vs. the control group (P= 0. 025). (2) After HIS, the arrangement of gastric mucosal epithelial cells in the model group was thinner than that in the control group (P= 0. 034). Additionally, the number of neutrophils in the lamina propria of the gastric mucosa in the model group was lower than that in the control group (P= 0. 016). The number of neutrophils in the colonic mucosa in the model group was higher than that in the control group (P= 0. 013). (3) After 9 days of HIS, Alpha diversity analysis showed that the number of operational taxonomic units in the fecal samples from the model group was significantly higher than that in the control group (P= 0. 001). The proportion of desulfovibrionaceae and helicobacteraceae in the model group was higher than that in the control group (P= 0. 011, P= 0. 047). Furthermore, the proportion of bacteroidaceae in the model group was significantly lower than that in the control group ( P= 0. 001). Conclusions Nine days of HIS induced a stable rat model of chronic stress in which chronic stress-induced immunosuppression occurred concomitantly with dysregulation of the gut microbial flora.