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ackground: Endothelial cells are very sensitive to mechanical force including microgravity and the morphological and functional changes in them are believed to be at the basis of weightlessness-induced cardiovascular deconditioning. It has been shown that the proliferation, migration, and morphological differentiation of endothelial cells play critical roles in angiogenesis. So far, the influence of microgravity on the ability of endothelial cells to foster angiogenesis remains to be explored in detail. The aim of this study was to investigate the effect of microgravity condition on VEGFR-2 and CD34 genes expression in human umbilical vein endothelial cells (HUVEC) in angiogenesis. Materials and Methods: In this study, HUVEC cells were purchased from Pastor Institute. We used a clinostat to simulate microgravity condition for 2, 24 and 72 hours. Real time PCR technique was used for gene expression analysis after extraction of RNA from cells. Results: Our results showed that microgravity for 72h leads to a significant increase (6 times compared with control group, p<0.001) in the VEGFR-2 gene expression. However, expression of CD34 did not change (p>0.05) with microgravity. Conclusion: Based on the results, microgravity has positive effect on angiogenesis and can be used to generate vascules for cell therapy of ischemic diseases and atherosclerosis. [ABSTRACT FROM AUTHOR]