Objective To explore the protection effects and molecular mechanisms of 17β-estradiol (17β-ESUB>2/SUB>) in high homocysteine (HHcy) induced injury of human osteosarcoma MG63 cells EM>in vitro/EM>. Methods Human osteosarcoma MG63 cells cultured EM>in vitro/EM> were treated with HHcy in different concentrations at different time after 17β-estradiol intervention treatment. The levels of reactive oxygen species (ROS ) were detected with a 2′,7′-dichloro-fluorescin diacetate probe (HSUB>2 /SUB>DCFDA ). The apoptotic and necrotic cells were determined by double nuclear staining with Hoechst 33342/PI. The expression levels of Caspase-3 and Bax were measured with Western blotting. Results 1.17β-ESUB>2/SUB>significantly suppressed the HHcy induced production of ROS in MG63 cells and the extent of suppression was positively associated with the dose and time. 2.17β-ESUB>2/SUB> significantly prevented MG63 cells from apoptosis or necrosis induced by HHcy and down-regulated t