VEGF is one of the most attractive candidates for modulating neurogenesis and cellular response to lesion. Although evidence indicated that reactive astrocytes in injury context and adult neural stem cells are major sources of VEGF, the mode of secretion, the intracellular targeting and the precise interactions of VEGF with the ECM remained elusive. In this work, we investigated the subcellular distribution of a VEGF-GFP fusion protein in polarized primary astrocytes in an in vitro wound-healing assay. These experiments revealed that substantial amounts of VEGF-GFP were attached to the outer cell membrane, partially linked to caveolae and shedded microvesicles. VEGF-GFP appeared also to accumulate behind the leading edges, spatially related to fibrillar adhesions, in association with fibronectin. Strikingly, we found that these two molecules exhibit similar expression patterns in reactive and SVZ astrocytes in vivo. Finally, we demonstrated that VEGF-GFP is also targeted to adherens junctions between astrocytes.