OBJECTIVE To investigate the effect of dantrolene on energy metabolism in rats with myocardial ischemia-reperfusion. METHODS Forty-eight male rats were randomly divided into 3 groups: control group, ischemia-reperfusion group and dantrolene treatment group. With a Langendorff model system, the hearts were perfused with Krebs buffer for 30 min as pre-ischemia control. For ischemia-reperfusion, the hearts were subjected to global ischemia for 30 min and reperfusion for 60 min. The dantrolene treatment group was perfused in the presence of 5 µmol/L dantrolene before ischemia. Tetrazolium chloride (TTC) staining, lactate dehydrogenase (LDH) release and hemodynamics were used to evaluate the tissue injuries. The effect of dantrolene on energy metabolism was evaluated by measuring the quantity of high-energy phosphates and the activity of 2 enzymes in purine salvage synthesis: hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and adenine phosphoribosyl transferase (APRT) by high-performance liquid chromatography (HPLC). RESULTS The myocardial infarct size and LDH release in dantrolene treatment group were lower than those of ischemia-reperfusion hearts [22.1% vs 25.3%, (70 ± 6) U/g vs (116 ± 10) U/g, both P < 0.05]. Dantrolene had no effect on the hemodynamics, except for a slight increase in coronary flow. The hearts receiving dantrolene showed a significantly higher levels of high-energy phosphates and a lower activity of HGPRT and APRT than those in the ischemia-reperfusion group [(7.63 ± 0.72) nmol×mg(-1)×min(-1) vs (12.42 ± 1.12) nmol×mg(-1)×min(-1), (4.14 ± 0.22) nmol×mg(-1)min(-1) vs (4.57 ± 0.39) nmol×mg(-1)×min(-1), both P < 0.05]. CONCLUSIONS Dantrolene is cardioprotective for ischemia-reperfusion injury through reducing infarct size and improving energy metabolism.