Objective:To study whether increase of O-GlcNAcylation in acute myocardial ischemia causes morphology change of myocardial cells by promoting activity of transcriptional factor CREB. Methods:HEK-293T cells were overexpressed with enzymes OGT and OGA,which regulate O-GlcNAcylation. Total O-GlcNAcylation levels and CREB phosphorylation were detected by Western-blot. Primary cultured rat myocardial cells were treated with drugs DON and PUGNAc to regulate intracellular O-GlcNAcylation levels. Cells morphology was observed by light microscope,and O-GlcNAcylation levels and phosphorylation of CREB were detected by Western-blot. Results:In HEK-293T cells and primary cultured rat myocardial cells,the CREB phosphorylation was positively correlated to the O-GlcNAcylation level. The elevation of O-GlcNAcylation in primary rat myocardial cells reduced the number of cells,but increased sive of the cells. Conclusion:O-GlcNAcylation regulates the activity of CREB positively. The elevated O-GlcNAcylation in acute myocardial ischemia is likely to cause the increase of myocardial cell size and the decease of cell density by promoting the activity of CREB,which may be one of the most important factors leading to myocardial remodeling.