The aim of this study was to investigate cardiac protection by tauroursodeoxycholic acid (TUDCA) in the development of diabetic cardiomyopathy (DCM) via suppression of cardiac apoptosis induced by endoplasmic reticulum stress (ER stress).At 2 weeks,and 2 and 5 months after diabetes onset with diabetic mouse model,cardiac remodeling and dysfunction were determined using echocardiography and hemodynamic evaluation and cardiac fibrosis was detected by Picric acid-Sirius red staining;ER stress signal pathway and apoptosis were detected by western blotting assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.Mechanism of cardiac protection by TUDCA was used by cell culture with embryonic rat heart derived cells (H9c2).Apoptotic cells and CHOP,the activated form of caspase-3 and caspase-12 delineate that diabetes mainly induced cardiac cell death at the early stage of diabetes (2 weeks),but not in the late stages (2 and 5 months).