Abstract: AIM To explore the role of p53 and Fas in human umbilical endothelial cells (HUVECs) apoptosis induced by ceramide. METHODS HUVECs were treated with different doses of C2-ceramide. The endothelial cells were cultured in vitro and treated with C2-ceramide alone or in combination with Fas-associated phosphalase-1 (FAP-1, an inhibitor of Fas) and PFT-α (an inhibitor of p53), respectively. The expression of Fas mRNA was measured by RT-PCR and the apoptosis of endothelial cells was detected by TUNEL staining. RESULTS C2-ceramide induces HUVEC apoptosis in a dose-dependent manner. FAP-1 (not PFT-α) inhibits the endothelial apoptosis by way of C2-ceramide. CONCLUSION It is via Fas, and not p53 that ceramide induces apoptosis of the endothelial cells.