Inhibition of the PI3K/Akt signaling pathway weakened the protective effects of GSP in ALI mice as well as blocked the GSP-induced M2a polarization of macrophages in primary lung macrophages of ALI mice and LPS-stimulated MH-S cells, suggesting that the promotion of M2a polarization by GSP to exert anti-inflammatory effects might be mediated by the activated PI3K/Akt signaling pathway. Here, GNAS is linked to acute respiratory distress syndrome.