Objective To investigate the effect of TRPM7 on the isolated myocardial ischemia reperfusion model in rats and to investigate the relationship between TRPM7 and PI3K pathway in the treatment of mild therapeutic hypothermia at 34 ℃.  Methods 108 healthy adult male Sprague-Dawley rats were divided into six groups and each group has 18 cases, SHAM group, do not do any processing; I/R group, with 37 ℃ during ischemia for 30 min and reperfusion for 120 min; I/R+2-APB group, with the addition of TRPM7 inhibitor 2-APB during reperfusion period; 34H+I/R group, with 34 ℃ of mild therapeutic hypothermia during reperfusion period; 34H+I/R+WORT group, with 34 ℃ of mild therapeutic hypothermia and the addition of PI3K inhibitor wortmannin during reperfusion period; ischemia/ reperfusion with mild therapeutic hypothermia and 34H+I/R+2-APB group, with 34 ℃ of mild therapeutic hypothermia and the addition of TRPM7 inhibitor 2-APB during reperfusion period. Then record the hemodynamics including the level of heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), ±dp/dtmax (maximum rate and minimal rate of rise of left ventricular) at the time point of baseline, 30 min before ischemia (T0); 30 min after reperfusion (T1); 60 min after reperfusion (T2); 90 min after reperfusion (T3); 120 min after reperfusion (T4). At the end of 120 min reperfusion, triphenyltetrazolium chloride staining (TTC) were used to evaluate myocardial infarction size; western blot were used to investigate TRPM7 expression; HE staining was used to observe the myocardial injury. Result In I/R group, the expression of TRPM7 and myocardial infarction area ［(52.74±1.25）%］ was significantly increased compared with Sham group［(13.87±1.17）%, P<0.05］; In I/R+2-APB group, the expression of TRPM7 and myocardial infarction area ［(42.85±1.19）%］ was decreased compared with Sham group and I/R group (P<0.05); In 34H+I/R group, the high expression of TRPM7 induced by ischemia reperfusion injury was reversed, the expression of TRPM7 was decreased as well as myocardial infarction area ［(34.63±0.72)%］ was decreased compared with Sham group and I/R group (P<0.05); In 34H+I/R+WORT group, the expression of TRPM7 was increased as well as myocardial infarction area ［(48.89±0.52)%］ was increased compared with 34H+I/R  group (P<0.05); In 34H+I/R+2-APB group, the expression of TRPM7 was decreased as well as myocardial infarction area compared with 34H+I/R+WORT group (P<0.05). There was no significant difference in TRPM7 expression and myocardial infarction area between 34H+I/R group and 34H+I/R+2-APB group ［(33.51±1.31）% vs. （34.63±0.72）%,P>0.05］. There was no significance difference of hemodynamic changes among the groups (P>0.05). Conclusion TRPM7 is highly expressed in myocardial ischemia reperfusion injury in a rat isolated heart model; Mild therapeutic hypothermia at 34 ℃ can inhibit the high expression of TRPM7 in myocardial ischemia reperfusion, and the protective effect is mediated by PI3K pathway in a rat isolated heart model.