Objective: To assess the efficacy and potential mechanisms of cardioprotection of ischemic postconditioning (IP ) combined with granulocyte colony stimulating factors (G-CSF) against acute myocardial ischemia-reperfusion injury in New Zealand rabbits. Methods: After ischemia by left vertebral artery (LVA) occlusion for 30 mins, male New Zealand rabbits were randomly assigned into four groups (n=15). Group 1: Ischemic-reperfusion alone(IR)group, thirty mins after LVA occlusion, reperfusion was immediately offered; Group 2: G-CSF group, animals were performed with the same operation as Group 1, and G-CSF at the dose of 10 μg·kg^-1 was daily simultaneously subcutaneously injected for 5 days 12 h after reperfusion; Group 3: ischemic postconditioning (IP)group, after 30 min ischemia and before reperfusion as Group 1,four episodes of 30 s reperfusion and 30 s occlusion were performed; Group 4: IP combined with G-CSF (IP+G-CSF)group, both IP and G-CSF intervention were offered as Group 2 and Group 3. Electrocardiogram (ECG) monitoring was consecutively applied during the whole operation. Blood was drawn from femoral vein to evaluate white blood cell count (WBC) and cardiac troponin I(cTnI) contents before operation and 7 d after reperfusion. Four weeks after the operation, ultrasound cardiography was used to monitor left ventricular remodeling and function. Infarcted myocardial sizes were calculated with triphenyltetrazolium chloride staining. Morphologic changes of cardiac muscle tissues were observed with optical microscope and transmission electron microscope. Results: Compared with IR alone group, IP group and IP+G-CSF group had significantly lower ST-segment resolutions (P<0.05). All groups treated with G-CSF showed more WBC 1 week later. The contents of cTnI after operation were significantly lower in G-CSF, IP and IP+G-CSF groups, compared with IR group. Left ventricular ejection fraction, infarcted myocardial size and morphologic observation demonstrated that IP, G-CSF and IP+G-CSF groups were significantly improved, compared with IR alone group. Among them, the magnitude of cardiac function improvement in IP+G-CSF group was the highest. Conclusion: Combining IP with G-CSF is beneficial to the alleviation of acute myocardial ischemia-reperfusion injury.