Objective To study the effect of hydroxysafflor yellow A(HSYA) in ameliorating the injury of myocardial ischemia/reperfusion(MI/R) in rats. Methods The model of MI/R injury was established in SD rats through ligation of left anterior descending coronary arteries for 30 min and reperfusion for 3 h. All rats were divided into sham-operation group(Sham group), model group(MI/R group) and HSYA group(5 mg/kg, each n=30). The changes of myocardial infarction area, hematoxylin-eosin(HE) staining, electrocardiogram(ECG), myocardial injury markers and inflammatory cytokines(IL-1, IL-6 and TNF-α) were observed. Results The myocardial infarction area was significantly smaller in HSYA group than that in MI/R group(P0.05). HE staining showed that myocardial cell morphology in HSYA group was similar to that in Sham group. The monitoring of hemodynamics and ECG showed that LVSP, +dp/dtmax,-dp/dtmax and heart rate(HR) were all higher in HSYA group than those in MI/R group(P0.05). The levels of creatine kinase MB(CK-MB) and cardiac troponin I(c Tn I) decreased in HSYA group compared with MI/R group(P0.05), and levels of IL-1, IL-6 and TNF-α decreased too in HSYA group compared with MI/R group(P0.05). Conclusion HSYA can reduce the severity and range of myocardial infarction, improve heart function, inhibit inflammatory cytokine release, and play a role of protecting and ameliorating myocardial ischemia.