Aim To observe the effect of extracellular nucleotide ATP on proliferation activity and biological function of human umbilical vein endothelial cell(HUVEC),and to explore its possible mechanism. Methods CCK-8 reagent kit was used to detect the effect of ATP intervening of different concentrations(0,1,5,10,50,100 μmol/L) and different time point(1~6 day) on proliferation of HUVEC;Flow cytometry was performed to detect apoptosis and cell cycle phase after treated with ATP as above;After treated with ATP of different concentrations(0,5,10,50,100 μmol/L) for 24 h,RT-PCR was performed to detect firstly the expression of P2 subtypes in HUVEC,secondly the expression of P2Y2,P2Y11,cyclinB1 and cyclinD1 and finally the expression of intercellular adhesion molecule(ICAM-1),vascular cell adhesion molecule(VCAM-1),endothelial nitric oxide synthase(eNOS). Results Compared with the control group,ATP groups(50 and 100 μmol/L) significantly inhibited the growth of HUVEC(P><0.01) and the inhibition of ATP(50 μmol/L) on HUVEC growth was time-dependent;ATP had no significant effect on HUVEC apoptosis,but high concentrations significantly increased the proportion of cells in S phase and diminished the proportion of cells in G2/M phase;ATP upregulated expression of ICAM-1,VCAM-1 in HUVEC in all concentration groups,and upregulated expression of P2Y2,11,eNOS and down-regulated expression of cyclinB1 only at high concentrations,while had no signifigant effect on cyclinD1 expression. Conclusion ATP at high concentrations(50,100 μmol/L) significantly inhibited HUVEC growth by blocking cell cycle in S phase and promoted expression of atherosclerosis-related adhesion molecules in HUVEC,which may be relevant to its role of up-regulating the expression of P2Y2,11 and down-regulating the expression of cyclinB1.