Objective To investigate whether ischemic post-conditioning (IPost) can ameliorate acute myocardial ischemia/reperfusion (I/R) injury in senescent rats and to compare the cardioprotective effects of ischemic post-conditioning between aged and adult rats. Methods A total of 32 male F344 rats were divided into adult (6 to 8 months) group and aged (18 to 20 months) group. After the rats were subjected to 30min ischemia by ligating the left anterior descending coronary artery (LAD), their hearts from each group were further randomized to receive standard, abrupt reperfusion (I/R group), or were post-conditioned with 4 cycles of 10s ischemia interspersed by 10s reperfusion immediately at the end of the ischemia (IPost group). Hemodynamic changes, such as mean arterial pressure (MAP) and rate-pressure product (RPP), and electrocardiogram (ECG) were recorded. Infarct size was measured by Evans blue and triphenyltetrazolium chloride (TTC) staining. At 120min of reperfusion, serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) were assayed. Results After 2 hours reperfusion, MAP and RPP were significantly higher in IPost group than in the corresponding I/R group for adult rats (P＜0.05). However, no significance was achieved in aged rats (P＞0.05). During the first 30min reperfusion, in adult rats, the arrhythmia scores were 1.0 and 3.5 respectively for the IPost group and I/R group with significant difference (P＜0.05). However, in aged rats, the arrhythmia scores were 2.0 and 3.0 for the IPost group and I/R group, but without significant difference (P＞0.05). Post obviously decreased the infarct size in the IPost group than in corresponding I/R group in both adult (by 52%) and aged cohorts (by 44%; P＜0.05 for both). The serum levels of CK and LDH were markedly lower in IPost group than in I/R group from both adult and aged rats (P＜0.05 for both). Conclusion IPost, as same powerful as to adult rats, reduces infarct size and decreases the release of myocardial enzymes in aged rats. What’s more, the post-conditioning attenuates myocardial stunning and reperfusion arrhythmia in adult rats, but these effects are not seen in the aged rats.