The aim of the present study was to evaluate the protective effect and possible mechanism of the total flavonoids (TFs) from Rosa Laevigata Michx fruit (RLMF) against hydrogen peroxide (H2O2) induced damage in human umbilical vein endothelial cells (HUVECs). The cell injury caused by H2O2 was protected by pretreatment with the TFs for 1 h. Compared with the model group, the TFs decreased S phase cells, suppressed nuclear morphological damage, inhibited the collapse of mitochondrial membrane potentials (Delta Psi m), attenuated excessive reactive oxygen species generation, reduced glutathione depletion, impacted the mitochondrial morphology change, decreased caspase-3, -9 activities, and decreased fragmented DNA. Further mechanism investigation showed that the TFs could increase the protein expressions of Procaspase-3, Bcl-2, and decrease the expressions of Bak, Bax, Bid and p53. Generally, the TFs from RLMF is an effective natural product for the treatment of cardiovascular and cerebrovascular diseases. (C) 2012 Elsevier Ltd. All rights reserved.