In this study, we revealed that methylallyl sulfone (AMSO2), the metabolite of active organosulfur compounds, had anti-inflammatory and antioxidant effect in a cigarette smoke extract (CSE)-induced lung injury model. Firstly, histological analysis showed that the CSE group exhibited lung injury compared with the control, which was alleviated by AMSO2. Secondly, we estimated its anti-inflammatory capacity. The results indicated that pretreatment with AMSO2 significantly decreased CSE-elevated tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum. Thirdly, AMSO2 also showed antioxidant properties through enhancing activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as reducing the level of malondialdehyde (MDA) and myeloperoxidase (MPO). Finally, we elucidated that AMSO2 alleviated inflammation and oxidative stress probably via suppressing ERK/p38 MAPK and inhibiting NF-κB expressions. In conclusion, we proposed that AMSO2 protected against the development of CSE-induced lung injury by reducing inflammatory cytokine levels and augmenting antioxidant activity via ERK/p38 MAPK and NF-κB pathways.