Aim To investigate the protective effects of isorhamnetin against oxidized low density lipoprotein (ox-LDL) induced apoptosis of endothelial cells and to figure out some of the underlying mechanisms of these effects. Methods Changes in cell viability were measured by the MTT method,the lactate dehydrogenase (LDH) release was evaluated by assay kits,and nitric oxide (NO) release was detected by the Griess assay. JC-1 staining was used to evaluate the mitochondrial membrane potential alteration,AO/EB staining was used to observe the morphological changes of apoptotic cells,and flow cytometry was employed to detect the apoptotic rate of the cells. RT-PCR was used to detect the lectin-like low density lipoprotein receptor-1 (LOX-1) and Caspase-3 mRNA expression. Results With the pretreatment by isohamnetin (10-7 μmol/L,10-6 μmol/L and 10-5 μmol/L),the decrease in endothelial cell viability and NO release as well as the increase in LDH induced by ox-LDL were significantly suppressed (P><0.05). The ox-LDL-induced mitochondrial membrane potential alteration and apoptosis were also considerably inhibited. All these suppressive effects exhibited concentration-dependant behaviors. Pretreatment by isohamnetin (10-7 μmol/L,10-6 μmol/L and 10-5 μmol/L) significantly (P><0.01) inhibited the ox-LDL induced LOX-1 and Caspase-3 mRNA upregulation in a concentration-dependant manner. Conclusions The results show the protective effects of isorhamnetin on endothelial cells from ox-LDL induced apoptosis. These effects may be related to the inhibition of ox-LDL induced LOX-1 and Caspase-3 mRNA upregulation and the decrease of NO release.