Abstract: Objective To explore the efficacy of somatostatin combined with magnesium sulfate in the treatment of patients with severe acute pancreatitis(SAP)and its effects on the levels of serum amylase(AMS), serum lipase(LPS)and inflammatory factors. Methods A total of 76 SAP patients were randomly divided into control group(n=38, treated with somatostatin)and observation group(n=38, treated with somatostatin and magnesium sulfate). The therapeutic effect and complications were compared between the two groups, and the levels of serum AMS, LPS and inflammatory factors before and after treatment were compared between the two groups. Results The total effective rate in the observation group was 94.74%, which was significantly higher than 78.95% in the control group(P<0.05). The levels of LPS and AMS after treatment in the observation group were significantly lower than those in the control group(P<0.05). The C-reactive protein(CRP), tumor necrosis factor-α(TNF-α)and interlenkin-6(IL-6)levels after treatment in the observation group were significantly lower than those in the control group(P<0.05). The incidence of complications in the observation group was 5.26%, which was significantly lower than 21.05% in the control group(P<0.05). Conclusion Somatostatin combined with magnesium sulfate is effective in the treatment of SAP patients, which can improve the levels of serum AMS and LPS, reduce the levels of inflammatory factors, and alleviate pancreatic injury.