Ｏｂｊｅｃｔｉｖｅ　The aim of the study was to investigate the association of change of calcitonin gene-related peptide（CGRP） in myocardium with increase of myocardial vulnerability in diabetic rats.　Methods　Forty male Sprague-Dawley（SD） rats， weighing 180 g-200 g， were randomly divided into control group （group C， n=20） and diabetes mellitus group （group DM， n=20）， in accordance with a random number table. Animals in group DM were fed with high sugar-fat diet， while those in group C were fed with standard laboratory diet. At the end of 4 weeks of high fat-sugar diet feeding， streptozotocin （STZ） was given （30 mg/kg， i.p.） to induce diabetes. At the end of 10 weeks after injection of STZ， animals in group DM and group C were randomly divided into ischemia/reperfusion（I/R） groups（group DM+I/R， group C+I/R） and sham operation groups（group DM+Sham， group C+Sham）respectively. Myocardial I/R was induced by occlusion and release of left anterior descending branch of coronary artery， under anesthesia. At the end of the reperfusion， histological immunofluorescence assay and enzyme-linked immuno sorbent assay（ELISA） were performed to evaluate the changes of CGRP. The infarct size of myocardium was examined using evans blue（EB） and triphenyltetrazolium chloride（TTC） staining.　Results　Cardiac CGRP positive nerve fibers mainly located in epicardium and the myocardium， especially around coronary vessels and endothelium. Compared with group C+sham［（4 369±310） ng/g］， the cardiac CGRP in group DM+sham was significant decreased［（2 271±339） ng/g］（P<0.05）. Although， After I/R， the amount of cardiac CGRP in diabetic and non-diabetic rats was significant up-regulated compared the sham operation group （P<0.05）， the content of cardiac CGRP in group DM+I/R was significant reduced［（3 138±423） ng/g］， compared to the group C+I/R［（6 192±406） ng/g］（P<0.05）. In the meantime， significantly larger infarct size was found in group DM+I/R（62.79%）， compared to the group C+I/R（43.35%）（P<0.01）.　Conclusions　Diabetes caused significant down-regulation of CGRP in myocardium of diabetic rats， which may be associated with extended injury caused by acute myocardial I/R while the underlying mechanism needs further investigation.