Introduction: The available evidence shows that perioperative oral thyroid hormone can significantly attenuate the postoperative decline in the serum hormone level and improve postoperative hemodynamic and prognostic parameters. However, there has been no study assessing the effects of preoperative oral different-dose thyroid hormone on serum hormone levels and myocardial ischemia-reperfusion injury (IRI) after cardiac surgery. Methods: Forty-eight healthy Wistar rats, aged 35 days, were randomly allocated into six groups: Group BC, Group C and four pretreatment groups in which the rats were given levothyroxine-sodium of 10 g, 20 g, 40 g and 80 g/100 g. On the eighth day, the serum thyroid hormone levels were determined and then an isolated heart ischemia-reperfusion model was established with a Langendorff apparatus. Results: Compared with Groups BC and C, serum thyroid hormone levels on the eighth day did not significantly change in Group 10 g, but were significantly increased in Groups 20 g, 40 g and 80 g. The cardiac enzyme myocardial-bound creatine kinase levels in the coronary effluent during reperfusion were significantly lower in Groups 10 g and 20 g and 40 g than in Group C. The recovery rates of +dp/dt(max) and -dp/dt(max) at 30 min during reperfusion were significantly lower in Groups 40 g and 80 g than in Groups 10 g and 20 g. Compared with Group C, myocardial expressions of heat shock protein 70 and myosin heavy chain were increased in the four experiment groups and myocardial expression of thyroid hormone receptor 1 was significantly increased in Groups 20 g, 40 g and 80 g. Conclusions: The pretreatment with enterally smaller doses levothyroxine-sodium does not significantly affect serum thyroid hormone levels and produces protection against myocardial IRI, whereas pretreatment with enterally larger doses of levothyroxine-sodium can only provide an attenuated or insignificant cardioprotection because of hyperthyroxinemia. Cardioprotection by levothyroxine-sodium pretreatment is probably attributable to increased myocardial expression of heat shock protein 70 and myosin heavy chain .