Danshen is commonly used in China for the treatment of atherosclerosis-related disorders such as cardiovascular and cerebrovascular diseases. Research shows that it also has immunostimulation properties. The present study evaluates the protective effect of danshensu, an active water-extractable component isolated from danshen, on an endothelial cell line (CRL-1730) treated with hydrogen peroxide (H(2)O(2)). Danshensu significantly inhibited endothelial cell viability induced by H(2)O(2). The treatment of endothelial cells with danshensu resulted in most cells being arrested in the S and G(2)/M phases of the cell cycle. The fraction of cells in G(0)/G(1) phase was markedly decreased by danshensu treatment compared to the control groups. The apoptosis was also markedly decreased after danshensu treatment. Additionally, danshensu restrains decreased nitric oxide level, increased the release of lactate dehydrogenase and expression of cluster of differentiation 40 (CD40) significantly. These results suggest that danshensu protects endothelial cells from the damage induced by H(2)O(2) through its CD40 anti-inflammatory approach and cell apoptosis inhibition.