OBJECTIVE To probe the protective effect and mechanism of different ways of preconditioning on vascular function of rats with hemorrhagic shock. METHODS The hemorrhagic shock model [40 mm Hg (1 mm Hg=0.133 kPa), 120 minutes] was reproduced in rat. The effect of preconditioning (ischemic or pharmacologic) on hyporesponsiveness of superior mesenteric artery (SMA) to noradrenaline (NE) induced by hemorrhagic shock was observed. RESULTS A loss of 5%-10% blood for preconditioning could not improve the survival rate of rat after hemorrhagic shock, while pinacidil preconditioning significantly increased the survival rate of rats with hemorrhagic shock lasting for 120 minutes. Preconditioning with 5% blood loss for 30 minutes increased the change in femoral artery blood pressure (BP) in rat at 0 minute after shock by the use of NE on mesenteric artery, while the same preconditioning for 24 hours could lower femoral artery BP previous to shock. Pinacidil preconditioning for 1 hour increased the changes in BP before hemorrhagic shock, while pinacidil preconditioning for 24 hours had no significant influence on the change in BP before and after shock. A loss of 5% of blood volume preconditioning for 24 hours improved the vascular responsiveness 120 minutes after hemorrhagic shock, and the change in diameter of SMA was increased significantly before and after the usage of NE (P<0.01). Although pinacidil preconditioning for 1 and 24 hours decreased the responsiveness of SMA to NE before hemorrhagic shock, the changes in diameter of SMA before and after the usage of NE decreased significantly (both P<0.05, respectively), and pinacidil preconditioning (1 and 24 hours) could increase the responsiveness of SMA to NE 120 minutes after hemorrhagic shock, with significantly increased changes of diameter of SMA before and after the usage of NE (both P<0.05). Glibenclamide could partly abolish the effects of pinacidil. CONCLUSION Although pinacidil (24 hours) could decrease the responsiveness of SMA to NE before hemorrhagic shock, it improves the vascular responsiveness of SMA to NE 120 minutes after hemorrhagic shock, and it improves the survival rate of hemorrhagic shock in rats, suggesting that pinacidil preconditioning (24 hours) could preserve the vascular function after hemorrhagic shock, and ATP sensitive potassium channel may be involved in the process.