Abstract： Objective To examine the relationship between the profound hypotension in endotoxic shock and the dynamic changes of nitric oxide (NO) and endothelin-1 (ET-1), so as to figure out which of the NO or ET-1 was more involved in the pathogenesis of endotoxic shock. And to investigate whether an offset of their opposite vasoactive effects would occur during endotoxic shock.Results Plasma ET-1 achieved its peak level at 60 min post-endotoxin, and then waned. Plasma NO-3 started rising at 120 min post-endotoxin, then progressive increase continued till the last measurement at 180 min post-endotoxin. The decrease of blood pressure was significant at about 120 min post-endotoxin and further went down until death. The changes of hemodynamics and NO showed a quite close temporal correspondence between the increase of NO and the decrease of blood pressure. L-NMA and phosphoramidon obviously reduced the plasma levels of NO and ET-1 to below their respective baseline levels, and showed transient effect of increase on blood pressure. Soon afterwards, however, the status of hemodynamics was aggravated. Dexamethasone just inhibited the excessive increase of NO and ET-1 during endotoxic shock without interfering their baseline levels and showed most beneficial effects on hemodynamics.Conclusions Both NO and ET-1 increase during endotoxic shock, but only the increase of NO has a close temporal correspondence with the decrease of blood pressure. It suggests a more important role of NO in pathogenesis of endotoxic shock. The increase of NO and ET-1 is different in time-process, which indicates that an offset of their opposite vasoactive effects would not occur. Intreference against the increase of NO and ET-1 during endotoxic shock is most beneficial when their baseline levels are maintained.