Acute respiratory distress syndrome (ARDS) is characterized by increased permeability of pulmonary blood vessels, leading to respiratory failure. Although VEGF is responsible for the vascular permeability, it remains unknown about the involvement of signaling for VEGFR1, a receptor for VEGF. We examined the role of VEGFR1 in pathology of ARDS. ARDS was created by an intra-tracheal injection of LPS to wild type (WT) mice and VEGFR1 tyrosine kinase deficient mice (TKKO). Compared with WT mice, TKKO mice displayed lower survival rates, increases in lung injury score, total protein concentrations, and pro-inflammatory cytokines including TNF and IL-6 in bronchial alveolar lavage fluids. Alveolar macrophages were diminished in both types of mice after LPS injection. Instead, neutrophils were extensively accumulated, and the number of neutrophils in TKKO mice was higher than that in WT mice. The same was true for macrophages recruited into the lung tissues. VEGFR1 was expressed in alveolar and recruited macrophages. These results suggested that VEGFR1 signaling attenuated LPS-induced acute lung injury by suppressing vascular permeability, cytokines production and neutrophil accumulation.