Our results demonstrated that anti-CD31-ORI-NPs targeting CD31 selectively accumulate in the endothelial cells of lung tissues where ORI-NPs release and bind to Keap1 and in turn activate Nrf2 signaling to suppress ROS generation and IL-6 expression, eventually to treat ALI/ARDS with high efficacy and low toxicity. This evidence concerns the gene PECAM1 and acute respiratory distress syndrome.