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Objective. To explore the influence of carbon dioxide pneumoperitoneum (CDP) on system inflammatory response syndrome (SIRS) and bacterial translocation (BT) in patients with bacterial peritonitis (BP) caused by acute appendicitis (AA). Methods. Eighty-six consecutive subjects were randomly divided into the laparoscopy and laparotomy groups (n = 44 and n = 42, respectively). The levels of white blood cells (WBC), C-reactive protein (CRP), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) of the 2 groups were tested preoperatively and at days 1, 2, and 4 after surgery. Blood and secretion culture was performed to verify whether septicemia or incision infection occurred, respectively. And the abdominal ultrasound or computed tomography scanning was used to diagnose peritoneal abscess for the suspected patients. The essential risk factors related to the aggravation of SIRS were analyzed through analysis of variance and binary logistic regression. Results. The postoperative blood levels of WBC, CRP, TNF-α, and IL-6 on day 4 in the laparoscopy group were significantly lower than those in the control group (all Ps < .05). The differences in incidence rates of septicemia and peritoneal abscess between the CDP and control groups were not statistically significant (P > .05). Nevertheless, the incision infection rate in the laparoscopy group was apparently lower than that in the control group (4.55% vs 19.04%, P = .047). Analysis of variance and binary logistic regression showed that the non-pneumoperitoneum, pathological type of appendicitis, and multidrug resistant infections were the 3 major risk factors for SIRS (the P values were .001, .019, and .012, respectively). Conclusion. It was found that CDP is safe for BP and could be a potential protective factor to mitigate BP effectively, indicating that the performance of laparoscopy operation under CDP is feasible to control SIRS; at the same time, CDP would not raise the incidence rate of BT.