Background: The immunologic repercussions due to cavity insufflation are the focus of great discussion. The aim of this study was to compare the inflammatory response and bacterial dissemination after laparotomy and abdominal CO2 insufflation in a murine model of peritonitis. Methods: Swiss mice were inoculated intraperitoneally with 0.5 ml of a solution containing 1 x 10 8 colonyforming units (CFU)/ml of Escherichia coli and were divided into three groups as follow: control (anesthesia for 30 min), laparotomy (2.5-cm midline incision for 30 min), and CO2 pneumoperitoneum (CO2 cavity insufflation for 30 min). The number of leukocytes, CFU/ml counting, and the levels of interleukin (IL)-6, tumor necrosis factor-a (TNF-a), and IL-10 were evaluated in blood, peritoneal, and pleural fluid samples obtained at 90 min and 18 h after the procedures. Results: The laparotomy group showed a greater bacterial dissemination to the blood, peritoneum, and pleural cavity and also greater neutrophil migration to the peritoneal cavity compared to the CO2 insufflated and control groups. The 24-h mortality was also significantly higher in the laparotomy group. The IL-6 levels showed a precocious rise in all groups submitted to bacterial inoculation at the 90-min time point. At the 18-h time point, IL-6 levels in the peritoneum were significantly higher in the laparotomy group than in the control or CO2 insufflated groups. At the same time, TNF-a levels were higher in the laparotomy and CO2 insufflated groups than in controls; IL-10 levels showed no differences among the groups. Conclusions: Our results suggest that cavity insufflation with CO2 is a more effective method of access, inducing less bacterial dissemination and also a less intense inflammatory response. Cavity insufflation with CO2 may present a good option for the surgical treatment of patients with bacterial peritonitis.2025-01-01