In Brief:
Our results indicate that trauma-hemorrhage induces lung injury (edema, neutrophil infiltration, increased cytokines, chemokines, and adhesion molecules expression); however, administration of 17β-estradiol after trauma-hemorrhage increased endothelial nitric oxide (NO) synthase expression/phosphorylation, protein kinase G-I activation, vasodilator-stimulated phosphoprotein phosphorylation and expression, and decreased lung injury. Thus, activation of the endothelial NO synthase-protein kinase G/vasodilator-stimulated phosphoprotein pathway by 17β-estradiol after trauma-hemorrhage protects against lung injury.