Bovine aortic endothelial cells (BAECs) were exposed to hydrostatic pressures of 50, 100, and 150 mmHg and changes in morphology and expression of vascular endothelial (VE)-cadherin were studied. After exposure to hydrostatic pressure, BAECs exhibited elongated and tortuous shape without predominant orientation, together with the development of centrally located, thick stress fibers. Pressured BAECs also exhibited a multilayered structure unlike those under control conditions and showed a significant increase in proliferation compared with control cells. Western blot analysis demonstrated that protein level of VE-cadherin were significantly lower under pressure conditions than under control conditions. Inhibition of VE-cadherin expression, using an antibody to VE-cadherin, induced the formation of numerous randomly distributed intercellular gaps, elongated and tortuous shapes, and multilayering. These responses were similar to those of pressured BAECs. The exposure of BAECs to hydrostatic pressure may therefore downregulate the expression of VE-cadherin, resulting in loss of contact inhibition followed by increased proliferation and formation of a multilayered structure.