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Objective To investigate the clinical effect of different doses of octreotide in the treatment of patients with severe acute pancreatitis (SAP). Methods A total of 154 patients with SAP who were admitted to our hospital from October 2018 to October 2022 were enrolled and randomly divided into observation group and control group, with 77 patients in each group. In addition to the conventional treatment methods including ulinastatin, the patients in the control group received intravenous drip of 0.6 mg octreotide, and those in the observation group received intravenous drip of 1.2 mg octreotide, once a day for 12 consecutive days. The two groups were compared in terms of overall response rate, proportion of patients with adverse reactions, time to clinical symptom disappearance, and time to normalization of blood amylase on day 12 of treatment, as well as the changes in the serum levels of inflammatory factors [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)], the levels of T lymphocytes, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, and modified CT severity index (MCTSI) score. Results The observation group had a significantly higher overall response rate than the control group (χ2=5.140,P0.05). Conclusion High-dose octreotide can effectively improve the treatment outcome of patients with SAP, enhance their immune function, and reduce inflammatory response with a favorable safety profile, and therefore, it holds promise for clinical application.