Objective：This study aims to investigate the effect of proton pump inhibitors on adhesion and inflammation of human umbilical vein endothelial cells（HUVEC）and its potential mechanism. Methods：Western blot and qRT-PCR were used to detect the mRNA and protein expression of interleukin-6（IL-6），intercellular adhesion molecule-1（ICAM-1）and vascular cell adhesion molecule-1（VCAM-1）in HUVECs after treating with 10 μmol/L lansoprazole for 0，24，48，72 and 96 h，protein levels of calcineurin（CaN）and nuclear factor of activated T cells（NFAT）were evaluated at the same time. In addition，protein levels of NFAT，IL-6，ICAM-1 and VCAM-1 were evaluated after treating with lansoprazole，CaN inhibitor FK506，and lansoprazole combined FK506 for the further research in mechanism. Results：Lansoprazole could time-dependently increase the expression of CaN and nuclear translocation of NFAT，and further increase the expression of IL-6，ICAM-1 amd VCAM-1. Calcineurin inhibitor could relieve the NFAT nuclear translocation and vascular inflammation induced by lansoprazole. Conclusion：Lansoprazole may induce endothelial cell inflammation and increase cell adhesion by activating CaN.