Abstract: To explore the effect of simulated microgravity (SMG) function on the proliferation, migration, and angiogenic capacity of human cerebral microvascular endothelial cells (hCMEC/D3), some methods were proposed to divide the hCMEC/D3 cells into comparison (CON) and 24h-SMG groups. The expression levels of Ang-2 and VEGFA were measured with ELISA. The impact of SMG function on cell migration was evaluated by scratch wound healing and tube formation assays, while the expression levels of VEGFR2, RAP1B, and ERK proteins were analyzed with Western-Blot. The results show that the 24h-SMG treatment can significantly improve the expression levels of Ang-2 and VEGFA. Scratch wound healing and tube formation assays demonstrate that SMG effect can enhance the migration and angiogenic capacity of hCMEC/D3 cells. Western-Blot analysis reveals that 24h-SMG can raise the relative expression levels of VEGFR2, Rap1B, and Braf, and can increase the phosphorylation levels of MEK1 and ERK1/2. The study draws a conclusion, SMG effect can promote the formation of cerebrovascular cells with activating the VEGFR2/RAP1B/ERK signaling pathway.