Objective To investigate the effect of section of pancreatic envelope combined with vacuum sealing drainage under laparoscopy on inflammatory mediators of patients with early severe acute pancreatitis (SAP). Methods Forty-two SAP patients were admitted to Foshan Hospital of Traditional Chinese Medicine in Guangdong Province from January 2008 to December 2016. That 22 patients underwent pancreatic membrane incision and vacuum sealing drainage under laparoscopy was in the experimental group, and that 20 patients underwent the routine pancreatic membrane incision and double tube drainage was in the control group. The venous blood was collected, the levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured before and after operation for 1, 3, 7 and 14 days, and the clinical therapeutic effects were observed in the two groups. Results With the prolongation of therapy, the levels of CRP, IL-6 and TNF-α were decreased continuously in both groups, the degrees of decrease of above indexes in experimental group were more significant than those in the control group, and the differences in these indexes between the two groups were statistically significant [CRP (mg/L): 1 day was 203.80±25.12 vs. 271.79±60.41, 3 day was 117.26±19.70 vs. 174.53±42.37; IL-6 (ng/L): 1 day was 40.63±3.38 vs. 57.10±11.46, 3 days was 23.14±3.51 vs. 46.87±10.69; TNF-α (ng/L): 1 day was 23.91±10.42 vs. 36.73±15.90, 3 days was 19.13±8.34 vs. 32.58±15.81, all P < 0.05]. There were no statistical significant differences in the levels of above indexes on 7 days and 14 days after treatment between the two groups (all P > 0.05). The therapeutic efficacy of the experimental group was significantly higher than that of the control group [95.45% (21/22) vs. 90.0% (18/20), P < 0.05]. Conclusion Under laparoscopy, pancreatic envelope incision combined with vacuum sealing drainage performed for early SAP patients can control the body inflammation more rapidly, reduce complications and shorten the disease course.