Peroxisome proliferator-activated receptor beta (PPAR-beta) is a ligand activated transcription factor belonging to the nuclear receptor superfamily. Recent evidence suggests that PPAR-beta has clearly defined roles in skin wound healing, inflammation and cell proliferation. However, little is known about the role of PPAR-beta in oxidative stress-induced apoptosis in human umbilical vein endothelial cells (HUVECs). In this study, a specific PPAR-beta ligand, L-165041, and antisense phosphorothioate oligodeoxynucleotides (asODNs) against PPAR-beta were used to reveal the role of PPAR-beta in oxidative stress-induced apoptosis. The results showed that H(2)O(2) at 0.5mM resulted in a marked increase of apoptosis and a significant down-regulation of PPAR-beta expression and activation in HUVECs. Moreover, L-165041 significantly inhibited H(2)O(2)-induced apoptosis (P<0.05) and asODNs against PPAR-beta markedly inhibited the de novo synthesis of PPAR-beta, which was accompanied by enhanced apoptosis induced by H(2)O(2) (P<0.05). These data demonstrated that H(2)O(2) down-regulated the expression and activation of PPAR-beta, which played important roles in H(2)O(2)-induced apoptosis in HUVECs.