Objective To observe the cardioprotective effects of α7nAChR agonist postconditioning on myocardial ischemia reperfusion injury in rat models in vivo. Methods Forty SD rats were randomly divided into four groups (n=10 in each group): sham group (S group), ischemia reperfusion group (IR group), ischemia preconditioning group (IPC group) and α7nAChR agonist postconditioning group (PNU group). Incidence of arrhythmia was recorded during the period of ischemia and onset of reperfusion. Serum concentrations of TNF-α, IL-6 were assayed at 30min and 180min after reperfusion, and serum concentrations of HMGB1 and TnI at 180min after reperfusion were tested in all groups. At the end of experiment, infarction sizes were assessed from excised hearts by Evans blue and triphenyltetrazolium chloride (TTC) staining. Results There was no significant difference in the baselines measurements of HR, MAP and RPP between the four groups. Compared to IR group, the infarct size and serum concentration of TnI in IPC group and PNU group were significantly reduced, the score of ischemic ventricular arrhythmias in IPC group was significantly decreased. The serum concentrations of TNF-α and IL-6 at 30 min of reperfusion and TNF-α and HMGB1 at 180 min of reperfusion in IPC group and PNU group were significantly lower than these in IR group. And the serum level of IL-6 at 180 min of reperfusion in PNU group was also significantly decreased compared to IR group. Compared to IPC group, the infarct size of PNU group was significantly increased, however the serum concentration of TnI of PNU group was significantly decreased. Although the serum concentration of IL-6 at 30 min of reperfusion in PNU group was significantly higher than that in IPC group, the serum concentrations of TNF-α at 30 min of reperfusion and TNF-α, IL-6 and HMGB1 at 180 min of reperfusion were significantly decreased. Conclusions In rat in vivo models of myocardial ischemia reperfusion injury, α7nAChR agonist postconditioning could inhibit the reperfusion-induced inflammatory response to realize the cardioprotection. However the effect of infarct size limiting induced by α7nAChR postconditioning is less powerful than that of ischemia preconditioning.