To explore the effect that Atropine, a competitive antagonist for the muscarinic acetylcholine receptor (mAChR), has on the response to LPS. Eight-week-old, male, B6 mice. Mice were treated with Atropine prior to, or after LPS challenge. Survival was monitored and analyzed via Kaplan-Meier analysis using the log-rank test. The effects of atropine on the inflammatory response (TNF-α, IL-6 and IL-10) were monitored at various time intervals following LPS injection in mice that were treated and not treated with atropine. Atropine administration prior to LPS induction of the inflammatory response resulted in reduced TNF-α and elevated IL-10 plasma levels without affecting the production of IL-6. This reduction in TNF-α levels was independent of the increase in IL-10 production. Atropine pretreatment improved the rate of survival from endotoxic shock in mice. The improved survival of mice after endotoxic shock could still be observed when atropine was administered several hours after LPS injection. The administration of atropine after injury may have a beneficial clinical effect.