Ceramide, a key molecule in sphingolipid metabolism and a candidate second messenger, has been shown to inhibit the activity of phospholipase D. This biochemical pathway has been implicated to regulate cell differentiation, apoptosis and cellular senescence. Ceramide is generated in response to a number of extracellular inducers (for example: TNF, IL-1 and Fas ligands etc.), and acts as a second messenger to mediate many of the effects of these inducers. HUVECs are the monolayer cells located inside the vein wall and play an important role in the regulation of vein physiology and blood function. It has been reported that the C6 ceramide can induce senescence of WI-38 HDF and promote the activity of beta-galactosidase, but, C2 ceramide has no such effect. In this study, we investigated the role of C6 ceramide in the senescence of HUVECs. 10 mumol/ml of C6 ceramide treatment for more than 72 hours can induce morphological alterations (such as: enlarged, flattened and irregular cell body), cell cycle arrested at G1 phase and the expression of the senescent histochemical marker-beta-galactosidase in HUVECs. These results showed that C6 ceramide could induce senescence-like changes of HUVECs. The detection of reactive oxygen species (ROS) and the anti-oxidative ability of the cells showed that the C6 ceramide induced senescence-like cells still have normal ability of anti-oxidation. Further investigations are ongoing.