Abstract: OBJECTIVE To explore the roles of nitric oxide(NO) and endothelin-1(ET-1) on the changes of hemodynamics following endotoxic shock in rabbits. METHODS 24 rabbits were divided into 3 groups: LPS control group, aminoguanidine (AG, specific inhibitor of inducible nitric oxide synthase, 20 mg·kg-1) +LPS group, PD-142893 (nonselective inhibitor of ET-1 receptors, 0.02 mg·kg-1)+ LPS group. Hemodynamic parameters and serum concentration of NO and ET-1 were monitored at baseline and 0.5, 1, 2, 4, 6 h after LPS injection in LPS control group. AG and PD-142893 were administrated at 1 h after LPS injection in AG+LPS group and PD-142893+LPS group. The hemodynamic parameters were monitored at baseline and 1, 2, 4, 6 h after LPS injection. RESULTS After LPS(1 mg·kg-1) injection, mean artery pressure (MAP) was decreased quickly and decreased 30.31% (achieved shock) at 0.5 h after LPS injection(P<0.05), then decreased steadily and decreased 40.61% at 6 h after LPS injection(P<0.05); maximum left ventricle systolic pressure (LVSP), maximum increase and decrease rate of left intraventricular pressure (±dp/dt max), were also decreased quickly at the early stage after LPS injection and had a transient increase a little later, then kept on decreasing smoothly; while left ventricle end-diastolic pressure (LVEDP) had no significant changes(P>0.05). After LPS injection, NO serum concentration presented double hump change, increased 72.50% and 95.83% respectively at 0.5 h and 6 h after LPS injection(P<0.05); ET-1 was increased significantly in the late stage and increased 68.74% at 6 h after LPS injection(P<0.05). Both AG and PD-142893 administration significantly improved hemodynamic parameters. CONCLUSIONS The production of NO and ET-1 may participate in the changes of hemodynamics following endotoxic shock. Inhibition of NO and ET-1 could significantly improve hemodynamic parameters.