Therefore, we aimed to elaborate the potential mechanism of Poldip2 in LPS-induced ALI, and to underline the relationship between Poldip2 and oxidative stress and the resulting inflammation in mice and A549 cells, consequently to reveal whether Poldip2 knockdown mediates inhibition of Nox4/Nrf2/NF-κB signaling pathway during acute lung injury. Here, POLDIP2 is linked to acute respiratory distress syndrome.