Abstract: Objective To investigate whether xenon preconditioning (PC) could protect immature myocardium against ischemia-reperfusion (I/R) injury in a dose-dependent manner and clarify the role of xenon PC on oxidative stress. Methods Forty-eight isolated perfused immature rabbit hearts were randomly divided into four groups (n=12): The sham group had the hearts perfused continuously for 300 min. In I/R group, the hearts were subjected to 60 min perfusion followed by 60 min ischemia and 180 min reperfusion. In 1 minimum alveolar concentration (MAC) and 0.5 MAC xenon PC groups, the hearts were preconditioned with 1 MAC or 0.5 MAC xenon respectively, following 60 min ischemia and 180 min reperfusion. The cardiac function, myocardial infarct size, mitochondrial structure, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in each group were determined after reperfusion. Results Compared with I/R group, both 1 MAC and 0.5 MAC xenon preconditioning significantly improved cardiac function (P<0.01), reduced myocardial infarct size (P<0.01) and mitochondrial damage, increased SOD activity and decreased MDA level (P<0.01). There were no differences between 1 MAC group and 0.5 MAC xenon group (P>0.05). Conclusion Xenon preconditioning at 0.5 and 1 MAC produce similar cardioprotective effects against I/R injury in isolated perfused immature heart.