Aim To investigate the protective effect of resveratrol (RSV) on myocardial ischemia/reperfusion (MI/R) injury in diabetic rats and its mechanism. Methods Type 2 diabetic rat model was induced by intraperitoneal injection of streptozotocin. After 2 weeks, diabetic rats were randomly divided into sham operation (sham) group, MI/R group and resveratrol (RSV) group. MI/R injury model was induced by ligation of the left anterior descending coronary artery. Lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I (cTnI), myocardial infarction area, cardiac systolic and diastolic function were measured in each group. Myocardial cell apoptosis index was detected by TUNEL assay. Western blot was used to detect the expressions of silent information regulator of transcription 1 (SIRT1), p53, acetylated p53 (Acetyl-p53), Bcl-2, Bax, and cytosolic and mitochondrial cytochrome C (Cyt C) and apoptosis inducing factor (AIF). HE staining was used to detect myocardial injury score. Results Compared with the sham group, myocardial infarction area, myocardial injury score, the expressions of myocardial LDH, CK, cTnI, Acetyl-p53, Bax, cytosolic Cyt C and AIF, and myocardial cell apoptosis index were significantly increased, while cardiac systolic and diastolic function were significantly decreased, expressions of Bcl-2, SIRT1, mitochondrial Cyt C and AIF were significantly reduced, in the MI/R group. Compared with the MI/R group, myocardial infarction area, myocardial injury score, the expressions of myocardial LDH, CK, cTnI, Acetyl-p53, Bax, cytosolic Cyt C and AIF, and myocardial cell apoptosis index were significantly decreased, while cardiac systolic and diastolic function were significantly improved, expressions of Bcl-2, SIRT1, mitochondrial Cyt C and AIF were significantly increased, in the RSV group. There was no difference of p53 expression in the three groups. Conclusion Resveratrol can attenuate MI/R injury by anti-apoptosis in diabetic rats, and its mechanism is related to SIRT1/p53 signaling pathway.