This experiment was carried out under the postulation that activation of an intracellular calcium-calmodulin complex may play an important role in myocardial injury induced by ischemia and reperfusion. Trifluoperazine[TFP], a calmodulin antagonist, was added to the potassium cardioplegic solution and used just before ischemia, and its protective effect from ischemic injury was investigated, using Langendorff rat heart model. TFP group had better post-ischemic functional recovery and lower post-ischemic contracture after 30 minutes of normothermic ischemia. Creatine kinase leakage was also decreased in TFP group but there was no statistical difference between control group and TFP group. We concluded that TFP has some protective effect from myocardial ischemic injury and its effect might be due to prevention of activation of intracellular calcium-calmodulin complex.