The inflammatory response plays a major role in ischemia-reperfusion injury (IRI). Considering that cholinergic stimulation can inhibit inflammatory response through the cholinergic anti-inflammatory pathway (CAP) and the alpha subunit-containing nicotinic acetylcholine receptor(alpha 7nAChR) expressed by immune cells is an important component of CAP, we assessed the effect of postconditioning with alpha 7nAChR agonist on systemic inflammatory response during the myocardial ischemia-reperfusion process in an in vivo rat model. Thirty Sprague Dawley rats were randomly divided into three groups: sham group, control group, and postconditioning with alpha 7nAChR agonist group (PP group). In the groups other than the sham group, the left anterior descending coronary artery was ligated for 30 min followed by a 180-min reperfusion. At the end of the experiment, the serum levels of troponin I, tumor necrosis factor alpha, interleukin-6, and high-mobility group box 1 were assayed, and the infarct size was assessed. The results showed that postconditioning with alpha 7nAChR agonist significantly attenuated the systemic inflammatory response to myocardial IRI, as evidenced by decreased serum levels of tumor necrosis factor alpha and high-mobility group box 1. Also, this treatment protected against myocardial IRI, as shown by reduced infarct size and serum troponin I level.