Vascular Endothelial Growth Factor (VEGF) is a highly conserved ligand that is involved in the regulation of angiogenesis and vasculogenesis, however, alternative roles of the ligand have been emerging. Organisms such as jellyfish and Drosophila contain VEGF homologs, yet they do not possess endothelial cells or a vascular system indicating that VEGF might have other primitive roles. In this current study we investigated how VEGF affects the post-natal development of the intestinal epithelial by either overexpressing VEGF or by reducing the bioavailability of VEGF with the overexpression of soluble VEGF receptor (sFLT-1) within the gastrointestinal tract. After three weeks of VEGF overexpression, mutant mice displayed an increase in villus height and proliferation in the transit-amplifying zone with the decrease of crypts per measured length and Lgr5 expression. On the other hand, sFLT-1 overexpressing mice had an increase in crypt depth with a decrease in villus height, proliferation in the transit-amplifying zone, crypts per measured length and reduced expression of Dll1 and Bmp4. Overall the availability of VEGF has the ability to alter the proliferation of progenitor cells in the crypt by either a direct or indirect signals. These studies reveal that by some means VEGF is altering the developing post-natal intestinal epithelium and proliferation. Largely, elucidating the interaction between VEGF and intestinal stem cells in intestinal development and differentiation may help to advance intestinal stem cell therapies in intestinal dysfunction or disease