Abstract: Objective To study the protective mechanism of captopril in diabetic cardiomyopathy by means of DNA microarray. Methods Rat models of diabetic cardiomyopathy were divided into test and control groups (n=5), and the rats in the test group were given oral captopril (1.5 mg/kg·b.w.) for 15 weeks. DNA microarray was prepared by blotting the PCR products of 4 000 rat cDNAs onto a specially treated glass slides. The probes were prepared by labeling the mRNA from the myocardial tissue of both control and test groups with Cy3-d UTP and Cy5-d UTP separately through reverse transcription. The arrays were then hybridized against the cDNA probes and the fluorescent signals scanned. Results The expression of genes in relation to fatty acid b oxidation, mitochondrial proton-electron coupling and oxidative phosphorylation, and that of dithiolethione-inducible gene-1 were up-regulated, while the dimethylarginine dimethylaminohydrolase gene expression was obviously lowered in the test group in comparison with those of the control group. Conclusion Captopril may protect the myocardial tissue through improving myocardial energy supply and depressing inflammatory reaction.