Schisandrin B (SchB), a dibenzocyclooctadiene derivative isolated from Schisandra chinensis, has been reported to have anti-inflammatory effects. However, the protective effects of SchB on cigarette smoke (CS)-induced lung inflammation remain unclear. This study was to investigate the effects of SchB on CS-induced lung inflammation in mice. The mice were exposed to CS to develop lung inflammation. SchB was given 1 h before CS exposure daily for five consecutive days. The levels of inflammatory mediators TNF-α, IL-1β, and IL-6 in bronchoalveolar lavage fluid (BALF) were measured in this study. SOD, GSH, MPO and MDA contents were also detected. Furthermore, the expression of Nrf-2 and NF-κB were detected by western blot analysis. Histopathological analyses showed that SchB had protective effects against CS-induced lung inflammation. The levels of inflammatory mediators TNF-α, IL-1β, and IL-6 in BALF were also inhibited by SchB. CS-induced MPO activity and MDA content were inhibited by SchB. The levels of SOD and GSH were up-regulated by SchB. SchB significantly inhibited CS-induced NF-κB activation and up-regulated the expression of Nrf2 and HO-1. In conclusion, these data suggest that SchB protects against CS-induced lung inflammation by activating Nrf2 and inhibiting NF-κB signaling pathway.