Radix Linderae, the dry roots of Lindera aggregata (Sims) Kosterm., is frequently used in traditional Chinese medicine. It contains alkaloids, volatile oils and sesquiterpene esters. In the present study, we investigated the therapeutic potential and underlying mechanisms of the total alkaloids from Radix Linderae (TARL) on collagen II (CII)-induced arthritis (CIA) in mice. TARL (50, 100 and 200mg/kg), orally administered on the same day of an antigen challenge for 20 consecutive days, alleviated disease severity in a dose-dependent manner but did not significantly affect body weights. The TARL treatment reduced the serum level of anti-CII IgG and suppressed the delayed type hypersensitivity evaluated by its effect against CII-induced ear swelling. TARL also protected joint destruction based on the evidence of reducing the histopathological scores. Furthermore, TARL suppressed CII- and concanavalin A-stimulated lymphocyte proliferation in popliteal lymph nodes, where are close to the affected joints in CIA. These data suggest that TARL is a potential therapeutic agent for rheumatoid arthritis that suppresses inflammation and protects joints from destruction.