BACKGROUND: Stem cell transplantation is a novel experimental strategy to treat heart disease, such as myocardial infarction. However, the exact mechanisms of this strategy remain obscure. The use of cDNA microarray can make it possible to simultaneously analyze gene expression profiles of the damaged heart injected by stem cell. METHODS: Microarray technology was used to evaluate the expression of 1,396 genes in a rat model of myocardial infarction. Gene expression changes were monitored in the left and right ventricle from a) 4 weeks(4wk-MI) after left anterior descending artery(LAD) ligation and b) 4 weeks(Tx4wk-MI) after stem cell injection into LV, 2 weeks after LAD ligation. RESULTS: Significant LV infarction was observed in all experimental animals. More than 670 genes and 330 genes were showed differential expression in response to 4wk-MI and Tx4wk-MI, respectively. In 4wk-MI animals, 74 genes(50 genes up-regulated; 24 genes down-regulated) exhibited significant differential expression in LV myocardium. In Tx4wk-MI animals, 83 genes(14 genes up-regulated; 69 genes down-regulated) exhibited significant differential expression in LV myocardium. These differentially expressed genes included those involved in cell structure, signal transduction, cell growth and maintenance, and apoptosis. CONCLUSIONS: Microarray gene profiling revealed candidate genes which may account for mechanism of stem cell transplantation strategy. This study may provide the new therapeutic modalities for enhancing myocardial performance and treating myocardial infarction.