In the present study, magnolol not only significantly inhibited the IL-1β-induced increase in IL-6, PGE2, MMP, and COX-2 protein levels, but also remarkably alleviated M. butyricum-induced arthritis in vivo by inhibiting the NF-κB and AP-1 signaling pathways, suggesting its potential therapeutic use as a novel topical anti-arthritic agent. The gene discussed is NFKB1; the disease is Arthritis.