Shuang-Huang-Lian (SHL) is a traditional Chinese compound formula prepared from Lonicerae Japonicae Flos, Scutellariae Radix and Fructus Forsythiae. In this study, we demonstrate the anti-inflammatory and anti-oxidative activities of SHL in lipopolysaccharide (LPS)-stimulated murine alveolar macrophages (MH-S). SHL significantly reduces the transcriptional and translational levels of iNOS and COX-2 as well as the production of NO and prostaglandin E2 (PGE2). It also suppresses the transcription and translation of inflammatory cytokines production, such as TNF-α, IL-1β and IL-6. These inhibitory effects mainly act via ERK1/2- and p38-mediated AP-1 rather than the NF-κB pathway. In parallel with the anti-inflammatory activity, SHL suppresses LPS-induced intracellular total ROS levels by weakening NADPH oxidase activity, enhancing SOD activity and increasing GSH content. In addition, SHL directly scavenges OH and O2(-). Thus, our study elucidates the anti-inflammatory and anti-oxidative mechanisms of SHL in LPS-stimulated MH-S.