Increased intraperitoneal pressure and insufflation of carbon dioxide during laparoscopy may cause sepsis by promoting systemic inflammation in patients with intra-abdominal inflammatory diseases. The influence of carbon dioxide and helium during laparoscopy on bacteremia, endotoxemia, the plasma concentration of tumor necrosis factor-alpha (TNF-alpha), TNF-alpha secretion ex vivo by peripheral blood mononuclear cells (PBMCs), and intraperitoneal abscess formation was investigated in an animal model. A standardized fecal inoculum was injected intraperitoneally, and rats underwent laparoscopy with either carbon dioxide (N = 20) or helium (N = 20) or no further manipulation (control group; N = 20). Bacteremia was significantly more common 1 hour after laparoscopy with CO2 than in animals receiving helium or the control group. Furthermore, helium use led to a significant decrease of bacteremia 1 week after intervention. Fecal inoculation caused significant leukocytopenia in all groups within 1 hour after intervention, with complete recovery only in the helium-treated group (p < 0.05). The TNF-alpha plasma concentration was significantly lower in the helium-treated group, and suppression of ex vivo production recovered only in the animals undergoing laparoscopy with helium (p < 0.05). The number of intraperitoneal abscesses was significantly lower after laparoscopy with helium (2+/-1.5) than after CO2 laparoscopy (6.3+/-5.1) or in the control group (5.2+/-4.8). Laparoscopy with CO2 increased systemic inflammation only slightly, while helium use was associated with a significant lower incidence of bacteremia and local and systemic inflammation compared with the control group.