Objective: To investigate the effect of glutamine on inflammatory cascade, serum high mobility group protein 1 (HMGB1) and heat shock protein (HSP) in patients with severe pancreatitis. Methods: From June 2016 to November 2018, 90 patients with severe pancreatitis were randomly selected from the general surgery department of our hospital. According to the random number table method, they were randomly divided into the research group and the control group, with 45 patients in each group. Patients in the control group were given routine treatment, such as fasting, nutritional support, antispasmolysis and pain relief, control of pancreatic secretion and anti-infection. Patients in the study group were treated with glutamine on the basis of the control group. All patients received continuous treatment for two weeks. To observe the clinical efficacy of the two groups of patients, inflammation [tumour necrosis factor alpha(TNF-alpha), interleukin 8 (IL-8) and interleukin 1 beta (1L-1 beta), interleukin 6 (IL-6) and C-reactive protein (CRP )J, serum levels of HMGB1, HSP, length of hospital stay, compare two groups of patients' serum amylase recovery time and duration of abdominal pain relief. Results: After treatment, the clinical efficacy of the study group was 93.33%, significantly higher than the 77.78% of the control group (P<0.05). Compared with before treatment, TNF-alpha, IL-8, IL-1 beta, IL-6 and CRP levels in both groups were significantly reduced after treatment, while the levels of all indicators in the study group were significantly reduced (P<0.05). After treatment, serum HMGB1 and HSP levels in the two groups were significantly lower than before treatment, and serum HMGBI and HSP levels in the study group were significantly lower than those in the control group (P<0.01). Compared with the control group, the hospitalization time, serum amylase recovery time and abdominal pain relief time were significantly reduced in the study group (P<0.01). Conclusion: Glutamine has obvious clinical efficacy in the treatment of severe pancreatitis, can significantly reduce the inflammatory cascade reaction of patients, reduce serum HMGB1 and HSP levels, and has good clinical application value.