Objective: To investigate the effect of Qingyi II formula on intestinal immune injury secondary to severe acute pancreatitis in rats. Methods: Fifty-six SD rats were randomly divided into sham operation group, SAP model group (SAP group), SAP model plus Qingyi II formula treatment group (Qingyi II group), and SAP model plus positive drug control group (glutamine group), with 8 rats in sham operation group and 24 rats each in the other groups. SAP model was induced by retrograde injected 5% sodium taurocholate into the bile-pancreatic duct. After operation, rats in Qingyi II group and glutamine group were subjected to gavage administration of Qingyi II formula (10 mL/kg, once per 6 h) and glutamine (0.15 g/100 g, once per 6 h) respectively, while those in the other two groups were given the same volume of normal saline instead in the same fashion. The specimen samples, except in sham operation group that were harvested at 6 h after operation, were harvested at 6, 12 and 24 h after operation in all of the other groups, with 8 rats in each time point. Then, the pathological changes in pancreatic and ileal tissues were observed, the serum concentrations of IL-1 and IL-10 were determined by ELISA assay, the HMGB1 mRNA expressions in the ileal tissues were detected by RT-PCR, and the apoptosis of CD3+, CD4+ and CD8+T cell subsets in the Peyer’s patches of the ileum were measured by flow cytometry. Results: Except in sham operation group, obvious and gradually aggravated pathological changes were seen in the pancreatic and ileal tissues in all of the other groups, which were all milder in both treatment groups than those in SAP group at each postoperative time point. Compared with sham operation group, the serum concentrations of IL-1 and IL-10, and HMGB1 mRNA expressions in the ileal tissues were all significantly and increasingly elevated in the remaining groups (all P<0.05), but the increasing amplitudes of IL-1 and IL-10 in both treatment groups were milder than those in SAP group at each postoperative time point (all P<0.05); the apoptosis rates of CD3+, CD4+ and CD8+T lymphocytes in the ileal tissues were all significantly increased in the remaining groups (all P<0.05), which showed an ascending trend in SAP group while a descending trend in either treatment group,and further, the apoptosis rates of these T lymphocytes in either treatment group were significantly lower than those in SAP group at each time point (all P<0.05). The difference in all above parameters showed no statistical significance between the two treatment group at the same time points (all P>0.05). Conclusion: Qingyi II formula can lessen the intestinal immune injury secondary to SAP in rats, and the mechanism may be associated with its down-regulating of HMGB1 expression in the ileum and thereby decreasing the apoptosis of T lymphocytes.