Abstract: OBJECTIIVE To observe the protective effects of chlorogenic acid against myocardial ischemia-reperfusion (I/R) injury and the effects of chlorogenic acid on the activation of MEK/ERK signaling pathway. METHODS Forty male SD rats were randomly divided into sham-operated group, I/R group, I/R+chlorogenic acid(50 mg·kg^-1) group, I/R+chlorogenic acid(50 mg·kg^-1)+MEK inhibitor(AZD6244, 15 μg·kg^-1) group, I/R+AZD6244(15 μg·kg^-1) group. Myocardial I/R model was established through ligation of the anterior descending branch of the left coronary artery for 30 min followed by reperfusion for 2 h after treatment for 2 weeks. The infarction area of myocardium were analyzed using triphenyltetrazolium chloride assay, serum levels of CK-MB, LDH, IL-6 and TNF-α were measured by ELISA kits, the expression levels of MEK and p-ERK were determined using Western blot assay. RESULTS Compared with sham-operated group, the infarction area of myocardium in I/R group was greatly increased, serum levels of CK-MB, LDH, IL-6 and TNF-α in I/R group were significantly increased, the expression levels of MEK and p-ERK were also greatly increased in I/R group (all P<0.05). Compared with I/R group, serum levels of CK-MB, LDH, IL-6 and TNF-α were significantly decreased in I/R+chlorogenic acid group, I/R+chlorogenic acid+AZD6244 group and I/R+AZD6244 group; the expression levels of MEK and p-ERK were significantly decreased in these groups(all P<0.05). CONCLUSION The protective effects of chlorogenic acid against myocardium against I/R injury in rats may involve in the inhibition of MEK/ERK signaling pathway activation.