Aim To investigate whether the release of endogenous calcitonin gene related peptide (CGRP) during preconditioning ischemic insult played an important role in myocardial ischemic preconditioning (IPC) in the intact rat model. Methods Plasma CGRP concentration at the end of first or third ischemic insult was determined with radioimmunoassay. Infarct size as a percentage of the area at risk was determined with nitro blue tetrazolium. Results Mean plasma CGRP levels at the end of first and third ischemic insult were markedly increased in the IPC compared with control(P< 0.01), and it was markedly higher at the end of third ischemia than first in the IPC group (P<0.05). IPC markedly reduced the incidences of ventricular arrhythmias during 30 min ischemia and 2 h reperfusion, which were markedly attenuated by pretreatment with CGRP PcAb. There was a marked reduction infarct size in IPC group (P<0.01) which was markedly attenuated by pretreatment with CGRP PcAb (P<0.01). Conclusion Calcitonin gene related peptide plays an important role in myocardial ischemic preconditioning.