Objective To investigate the clinical efficacy of combination of Xuebijing with ERCP in the treatment of severe acute pancreatitis complicated by sepsis and its influence on gastrointestinal function and inflammatory factors. Methods A total of 98 patients with severe acute pancreatitis and sepsis who were hospitalized in the intensive care unit of our hospital from February 2019 to September 2020 were selected and divided into two groups by random number table method, including 50 cases in the observation group, 48 cases in the control group. Patients in both groups were given symptomatic supportive therapy. Patients in the control group underwent endoscopic retrograde cholangiopancreatography(ERCP), and patients in the observation group were treated with Xuebijing injection for 7 days on the basis of the treatment of the control group. The clinical efficacy of the two groups of patients after the end of treatment was compared, the levels of C-reactive protein and white blood cells of the patients were detected to compare the remission of infection, and the changes in the levels of gastrointestinal hormones and inflammatory factors in the two groups were monitored and compared. Results After 7 days of treatment, the clinical recovery rate(62.0%) of the observation group was significantly higher than that of the control group(37.5%)(P＜0.05). After treatment, the observation group's hospital stay, time to return to normal body temperature, and recovery Spontaneous defecation time, relief time of abdominal pain and improvement time of abdominal distension were significantly shorter than those of the control group(P＜0.05). Compared with the patients in this group before treatment, the serum levels of PAMY, CRP, WBC and APACHEⅡ score of the two groups of patients were significantly reduced after treatment(P＜0.05). Compared with the control group after treatment, the observation group The levels of PAMY, CRP, WBC and APACHE Ⅱ score were significantly reduced(P＜0.05). Compared with patients in this group before treatment, the mass concentrations of APTT, PT, and TT were significantly reduced after treatment in the two groups, and the mass concentration of FIB was significantly increased(P＜0.05). Compared with the control group after treatment, the APTT, PT, TT mass concentration of the observation group was significantly reduced, and the FIB mass concentration was significantly increased(P＜0.05). After treatment, the observation group had B cells, NK cells, T lymphocyte subsets(CD4+, CD8+) and CD4+/CD8+ valueswere significantly higher than those of the control group(P＜0.05); compared with this group before treatment, the serum MTL levels of the two groups were significantly increased, and the GAS levels were significantly reduced(P＜0.05), and the serum MTL level of the observation group was significantly higher than that of the control group, and the GAS level was significantly lower than that of the control group(P＜0.05). Compared with this group before treatment, the serum levels of IL-6 and IL- 8 and TNF-α levels were significantly reduced(P＜0.05). Compared with the control group, the serum levels of IL-6, IL-8 and TNF-α in the observation group were significantly reduced(P＜0.05). Conclusion Xuebijing combined with ERCP in the treatment of severe acute pancreatitis with sepsis, the clinical effect is definite, which can effectively control infection, reduce inflammatory cytokine levels, and improve the gastrointestinal function of patients. The overall clinical effect is better than ERCP alone.