Introduction: Microglia are closely communicating with endothelial cells and involved in cerebrovascular disease. In brain arteriovenous malformation (bAVM), microglia are highly detected in the vascular walls and brain parenchyma, however, the role of microglia in bAVM are not clear. Meanwhile, soluble endoglin (sENG) has been involved in inflammation and endothelial dysfunction in bAVM. Therefore, we hypothesized that microglia mediate sENG-induced endothelial dysfunction in bAVM. Methods: sENG was subcutaneously injected to mice with VEGF overexpression in the brain. After latex casting to visualize brain vasculature, dysplastic capillaries were measured by Zen software. Microglia was detected by iba-1 staining. In in vitro , sENG or vehicle was treated in BV2 microglial cell line and the cultured media from BV2 (BV2-CM) were transferred to primary mouse brain endothelial cell (EC). We determined the expression of inflammatory/angiogenic factors in the BV2 and EC, and tested the tube formation in the EC. Results: The sENG with VEGF induced dysplastic/enlarged capillaries in the mouse brain (8567 μm 2 ± 2797 vs 2584 μm 2 ± 763, p <0.01) and activated microglia were accumulated around the abnormal vessels. In in vitro study, sENG increased inflammatory cytokines (TNF-α and IL-6) and angiogenic mediators (MMP-9 and VEGF-A) in BV2 cells. The sENG-treated BV2-CM significantly increased angiogenic factors (Notch-1 and TGF-β) but decreased an anti-angiogenic factor (IL-17RD), and it was accompanied with increased pERK1/2 in EC. In addition, we observed that tube formation is significantly increased in EC treated with sENG-treated BV2-CM. Conclusion: The study shows that sENG-stimulated microglia released inflammatory and angiogenic factors and it regulates endothelial functions. It suggests that microglia may contribute to sENG-induced dysplastic capillary via regulating inflammatory and angiogenic factors.