Vascular Endothelial Growth Factor (VEGF-A), has been implicated in the pathogenesis of many chronic lung diseases including Idiopathic Pulmonary Fibrosis (IPF) in which failure of essential tissue repair occurs. Here it is demonstrated that IPF is associated with an increased expression of an antiangiogenic VEGF-A splice variant in both IPF lung tissue and isolated IPF lung fibroblasts. In a mouse model of pulmonary fibrosis, alveolar type two cell (ATII) specific deficiency of VEGF-A or constitutive over-expression of VEGF-A165b inhibited the development of pulmonary fibrosis as did treatment with intraperitoneal delivery of VEGF-A16Sb to wild-type mice. These results indicate that changes in VEGF-A expression sourced from ATII cells, namely the ratio of VEGFAxxxa to VEGF-Axxxb, are critical in the development of pulmonary fibrosis and may be a paradigm for the regulation of tissue repair.