Abstract: With the development of aviation, the health of astronauts in microgravity has aroused more attention. It has been reported that vascular endothelial cells are highly sensitive to gravity. The endothelium is located in a strategic anatomical position within the blood vessel wall and thereby plays a crucial role in maintaining physiological function, such as the integrity of the vasculature, material transfer, endocrine function and so on. However, the mechanism underlying the changes of endothelial cells function and structure induced by microgravity still remain to be fully elucidated. As the deepening research of aerospace medicine, it has been found that the cytoskeleton is very sensitive to the change of gravity. In microgravity, the vascular endothelial cell cytoskeleton will change, showing as the destruction of microfilament and microtubule, which may result in the changes of cell proliferation, apoptosis and signal transduction function. The progresses in effects of microgravity or simulated microgravity on vascular endothelial cells functions regulated by cytoskeleton are reviewed in this article.