We sought to determine whether taurine could specifically protect against coronary artery disease during an atherogenic diet and whether taurine affects the lipid profile, metabolites of methionine, and endothelial atherogenic systems. Rabbits were fed one of the following diets for 4 weeks: (1) control diet; (2) 0.5% cholesterol+1.0% methionine; or (3) 0.5% cholesterol+1.0% methionine+2.5% taurine. Endothelial function was examined, and the left main coronary artery atherosclerosis was quantified by stereology and semiquantitative immunohistochemistry to determine the endothelial expression of proteins related to the NO, renin-angiotensin, endoplasmic reticulum, and oxidative stress systems, as well as apoptosis. Taurine normalized hyperhomocysteinemia (P<0.05) and significantly reduced hypermethioninemia (P<0.05) but not lipidemia. The intima:media ratio was reduced by 28% (P=0.034), and atherosclerosis was reduced by 64% (P=0.012) and endothelial cell apoptosis by 30% (P<0.01). Endothelial cell CCAAT/enhancer binding protein homologous protein was normalized (P<0.05). Taurine failed to improve hyperlipidemia, endothelial function, or endothelial proteins related to the NO, renin-angiotensin, and oxidative stress systems. Taurine reduces left main coronary artery wall pathology associated with decreased plasma total homocysteine, methionine, apoptosis, and normalization of CCAAT/enhancer binding protein homologous protein. These results elucidate the antiapoptotic and antiatherogenic properties of taurine, possibly via normalization of endoplasmic reticulum stress.