Activation of the complement system is an integral part of the initiation and maintenance of the inflammatory process such as that occurring in traumatic shock, and is considered responsible for much of the trauma-induced microvascular injury. We investigated the effects of early complement blockade induced by a C1 esterase inhibitor (C1 INH) in a rat model of traumatic shock. Pentobarbitalanesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by marked hypotension and a 83.3% mortality rate with a mean survival time of 157.5 ± 26 min. Accompanying these effects were significant endothelial dysfunction and elevated intestinal myeloperoxidase activity. Treatment with C1 INH 15 mg/kg administered intravenously 10 min post-trauma, increased survival rate to 66.7% (p < .05), and prolonged survival time to 248 ± 27 min (p < .05). C1 INH significantly preserved the endothelium-dependent relaxation to acetylcholine and attenuated the increases in myeloperoxidase activity in C1 INH-treated rats compared with untreated trauma rats (p < .05). Our results suggest that complement activation plays an important role in tissue injury associated with trauma, and that its inhibition at an early step in the complement cascade through a C1 esterase inhibitor is beneficial in rats experiencing traumatic shock. The mechanisms of the protective effect of C1 INH involves preservation of vascular endothelial function and diminished neutrophil accumulation leading to reduced neutrophil-mediated tissue injury.