Abdominal insufflation (AI) by carbon dioxide has been shown to decrease the rate of bleeding in different swine models of abdominal organ injuries. With development of appropriate tools, AI could be used to control bleeding temporarily in the prehospital setting. Concerns have been raised about the inflammatory response to AI, which could damage organs at a later stage despite initial hemostasis. We hypothesized that AI controls bleeding without inducing an unfavorable inflammatory response. An experimental splenic injury was caused in 28 Yorkshire pigs, which were randomized to: 1) standard resuscitation (n = 14) with crystalloids to a mean arterial pressure of 60 mm Hg, or 2) standard resuscitation and AI (n = 14) to an abdominal pressure of 20 cmH2O. The experiment lasted for 30 minutes, and intra-abdominal blood loss was measured. Blood serum interleukin 1beta (IL-1beta), transforming growth factor beta1, and lung tissue heat shock protein 70 gene expression were measured at 0, 15, and 30 minutes, as markers of the inflammatory response. All animals survived to the end of the experiment. Total blood loss was significantly less in the AI group compared with the other standard resuscitation animals (733 +/- 76 vs 1094 +/- 153 mL, P = 0.049). The pH at the end of the experiment was significantly lower in the AI group (7.28 +/- 0.02 vs 7.44 +/- 0.05, P < 0.01) but there was no difference in lactate levels (1.5 +/- 0.4 vs 1.7 +/- 0.3, P = 0.7). Similarly, there was no difference in IL-1beta, transforming growth factor beta1, or lung tissue heat shock protein 70 gene expression between the two groups at any time point, although there was a trend towards lower IL-1beta levels in the AI group. Our conclusion is that AI reduces blood loss from splenic injury without a measurable effect on the early inflammatory response in a clinically relevant animal model.