Atropine is a naturally occurring alkaloid extracted from the plant Belladona atropina, atropine and related compounds compete with acetylcholine for a common binding site on the muscarinic receptor. In previous studies we have found that atropine attenuates TNF-alpha production and upregulates IL-10 and also increases survival when given 10 minutes before lipopolysaccharide (LPS) administration. In this study we determine if other time points would also effect cytokine production and survival. To determine atropine’s therapeutic window in our model of LPS, C57BL/6J (B6) mice were injected with atropine (1mg/kg) at -10 min, 0 min, +10 min or + 30 min with respect to LPS (15mg/kg) administration. Blood was harvested 1.5 hours after LPS administration and TNF and IL-10 levels were analyzed by ELISA. In a separate experiment a mortality experiment was conducted with the same protocol mentioned above except that the final endpoint was mortality. Atropine treated animals at -10, 0, and +10 min had suppressed TNF levels while IL-10 correlated again with increased levels within these groups (P<0.05). The group that received atropine thirty minutes after LPS administration failed to suppressed TNF levels or upregulate IL-10 levels. Atropine treated animals at -10 min, 0 min, +10 and at even +30 min had an increase in survival ( 75%, 67%, 58%, and 58% respectively vs 0% in the LPS control, (P=<0.001). Our cytokine data correlated with increase in survival for all groups, except for the +30 minutes groups in which the cytokine data failed to reach statistical significance compared to the LPS control group. These findings suggest that atropine attenuates the inflammatory response and increases survival from endotoxic shock in rodents. Further studies should investigate the mechanism and determine if atropine might be useful in the treatment of critically ill patients.