Corynoline, isolated from Corydalis bungeana Turcz, has been reported to possess anti-inflammatory and antibacterial activities. In this study, we aimed to explore the treatment effect of corynoline on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. In the present study, the signaling pathways were measured by Western blot analysis. The levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assays (ELISA). Additionally, the effects of corynoline on LPS-induced myeloperoxidase (MPO) activity was examined. The results showed that corynoline markedly inhibited LPS-induced neutrophils influx, MPO activity, and inflammatory cytokines IL-1β, TNF-α and IL-6 release. Corynoline also attenuated lung histopathological changes induced by LPS. Furthermore, corynoline inhibited LPS-induced NF-κB activation. In addition, corynoline up-regulated the expression of Nrf2 and HO-1 in a dose-dependent manner. The data suggest that corynoline has a treatment effect on LPS-induced ALI in mice by inhibiting inflammatory response.