Objective To examine the effects of carbon dioxide (CO2) pneumoperitoneum on local pancreas pathological changes, serum levels of amylase, IL-1, IL-6, and the positive rate of dissolubility adhesion molecule (CD11a/CD18 and CD11b/CD18) expression in rats with severe acute pancreatitis (SAP). Methods Fifty healthy male SpragueDawley (SD) rats were randomly divided into 3 groups: CO2 pneumoperitoneum group (n=20): SAP was induced by injecting 5% sodium taurocholate through retrogradely common biliopancreatic ducts via duodenal papilla， and then CO2 pneumoperitoneum was established at a pressure of 12 mm Hg (1 mm Hg=0.133 kPa) for 30 min; SAP group (n=20): The rats were treated as same as CO2 pneumoperitoneum group, except CO2 pneumoperitoneum； Simple operation group (n=10): Laparotomy was performed and nothing was done to duodenum and pancreas except for moving them softly. The blood samples were collected for examining serum levels of amylase, IL-1, IL-6, and the positive rates of CD11a/CD18 and CD11b/CD18 expression, and histopathologic examination of pancreas was performed. Results Compared with simple operation group, the pancreatic pathologic histology score, serum levels of amylase, IL-1, IL-6, and the positive rates of CD11a/CD18 and CD11b/CD18 expression were significantly higher in CO2 pneumoperitoneum group and SAP group (P=0.000). The levels of IL-1 and IL-6 were significantly lower in CO2 pneumoperitoneum group as compared to SAP group (P=0.000). There was no significant difference between CO2 pneumoperitoneum group and SAP group in pancreatic pathologic histology score (P=0.294), the level of serum amylase (P=0.073), the positive rates of CD11a/CD18 (P=0.155) and CD11b/CD18 expression (P=0.201). Conclusion CO2 pneumoperitoneum has inhibitory effect on the levels of IL-1 and IL-6, rather than the positive rates of CD11a/CD18 and CD11b/CD18 expression in SD rats with SAP.