Objective To investigate the protective effect of adenosine A1 receptor agonist (2-chloro-N6-cyclopentyladenosine, CCPA) delayed preconditioning on myocardial ischemia reperfu-sion injury and the potential mechanism in rabbits. Methods Thirty New Zealand male white rabbits were randomly assigned to 3 groups:a control group, an I/R group, and a CCPA group. CCPA group was given CCPA 0.1 mg/kg before the myocardial ischemia. Twenty-four hours later I/R group and CCPA group underwent 40 min of coronary occlusion followed reperfusion for 2 h. At the end of the reperfusion, blood samples were taken from the arterial line for determining the plasma level of malondialdhyde and superoxide dismutase activity. The infarct size and area at risk were de-fined by Evans and TIC staining. The heart was harvested and levels of metallothionein (MT) were determined by Western blot, and ultrastructures were observed under the electron microscope. Results The MT level of CCPA group was significantly higher than that of the I/R group (P<0.05). CCPA significantly reduced the infarct size (22.1%±3.8% in the CCPA group) of the left yen-tricular area at risk as compared with the control (41.8%±4.3% in the I/R group,P<0.05). The injury of I/R group was worse than that of the CCPA group under the light microscope. CCPA group had higher superoxide dismutase and lower malondialdhyde than those of the I/R group. Con-clusion CCPA can increase the level of metallothionein during ischemia-reperfusion, which may be part of the molecular mechanism of CCPA delayed preconditioning on cardioprotection.