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Objective: To explore protective effect of rosiglitazone on myocardial ischemia reperfusion injury. Methods: A total of 48 male SD rats were randomly divided into control group (A), I/R group(B),high dose of rosiglitazone (C), low dose of rosiglitazone (D). Plasm concentration of creatine kinase (CK), CK-MB, hsCRP, Superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), nitric oxide (NO) and endothelin (ET) were measured 1 h later after I/R. 24 h after I/R hearts were harvested to observe pathological and ultrastructural changes. Immunohistochemistry and west blotting was used to test CD40 expression in myocardial tissue. Area of myocardial infarction were tested, arrhythmia rate during I/R was recorded.Results:Plasm concentration of creatine kinase (CK), CK-MB, hsCRP, NO, MDA and ET were decreased in group C, D compared with group B. Plasm concentration of T-SOD and GSH-Px was increased significantly in group C, D compared with group B. Compared with group B, pathological and ultrastructural changes in group C, D were slightly. Myocardial infarction area and arrhythmia rate were lower in group C, D compare with group B. Conclusions: Rosiglitazone can protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration, inhibit inflammatory reaction, improve endothelial function, reduce oxidative stress and calcium overload.