Aim To explore the effect of different P2Y12 receptor antagonist ticagrelor and clopidogrel on inflammatory factors and myocardial infarct size in ischemia reperfusion rats. Methods 48 healthy male SD rats, weighing 250 ± 306 g, were randomly divided into four groups (n=12):sham operation group :after thoracotomy threading, do not tighten the ligature; control group :tighten the ligature for 45 min, then relax the ligature followed by reperfusion; clopidogrel group :after left anterior descending artery ligation immediately inject clopidogrel 90 mg/kg from the tube per day. Ticagrelor group:after left anterior descending artery ligation, immediately inject ticagrelor 150 mg/kg per day. Observed inflammatory cytokines in the serum and cardiac function after 24 hours and one week, and the left ventricle (LV), ischemic risk zone (AAR) and infarct area (IS) area of four groups, with AAR/LV and IS/AAR indicating the degree of myocardial infarction. Results The concentration of inflammatory factors before surgery of four groups was not statistically significant (P>0.05); Compared with the control group , in the clopidogrel group and ticagrelor group, the concentrations of CRP, IL-1, IL-6, TNF-α after 24 hours and seven days significantly decreased, the difference was statistically significant (P<0.05);After 24 hours, inflammatory cytokines concentration were different in ticagrelor group and clopidogrel group, but not statistically significant (P>0.05); 7 days later, concentrations of inflammatory cytokines in the ticagrelor group and clopidogrel group was significantly decreased, the difference was statistically significant (P<0.05). There was no infarcted area in sham operation group, after 24 hours and after 7 days in clopidogrel group and control group, ischemic risk zone and infarct area was not statistically significant (P>0.05); Compared with control group and clopidogrel group, in the ticagrelor group, after 24 hours and 7 days, the difference of ischemic infarct area and danger zone was statistically significant(P<0.05); Conclusions P2Y12 receptor antagonist ticagrelor and clopidogrel could significantly reduce the concentration of inflammatory factors in ischemia-reperfusion injury rats, ticagrelor instead of clopidogrel can further reduce the risk area and infarct area in ischemia-reperfusion injury rats.