The injury of endothelial cell is the critical event of vascular disease. In endothelial cell, oxidative stress is regarded as critical to pathogenic factors in endothelial cell injury and apoptosis. Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as "Danshen" in traditional Chinese medicine for treating cardiovascular disorders, but the mechanism by which it exerts the protective effect is not well established. The present study was designed to test the hypothesis that tanshinone IIA can inhibit hydrogen peroxide ( H(2)O(2) )-induced injury and unravel its intracellular mechanism in human umbilical vein endothelial cells (HUVECs). In this study, HUVECs were treated with tanshinone IIA in the presence/absence of H(2)O(2) . The protective effects of tanshinone IIA against H(2)O(2) were evaluated. Our results show that HUVECs incubated with 200 μM H(2)O(2) had significantly decreased the viability of endothelial cells, which was accompanied with apparent cell apoptosis, the activation of caspase-3 and the upregulation of p53 expression, which was known to play a key role in H(2)O(2) -induced cell apoptosis. However, pretreatment with tanshinone IIA (3-10 μM) resulted in a significant resistance to H(2)O(2) -induced apoptosis. In addition, pretreatment with tanshinone IIA decreased the activity of caspase-3 and p53 expression. Tanshinone IIA also induced activating transcription factor (ATF) 3 expression; while knockdown of ATF-3 with ATF-3 siRNAsignificantly reduced tanshinone IIA's protective effect. In conclusion, the present study shows that tanshinone IIA can protect endothelial cells against oxidative injury induced by H(2)O(2) , suggesting that this compound may constitute a promising intervention against cardiovascular disorders and ATF-3 may play an important role in this process.