Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by the inflammatory synovitis and the destructive cartilage and bone. Triptolide is a biologically active component purified from the Chinese herbal plant Tripterygium wilfordii Hook F (TWHF), which has presented benefits for the treatment of RA. In the current study, we investigated therapeutic effects of Triptolide in collageninduced rheumatoid arthritis rat model. Administration of Triptolide (30 μg/kg) was used to treat Collagen-Induced Arthritis (CIA) rat model by the subcutaneous injection of bovine type II collagen. Our data demonstrated the triptolide treatment significantly reduced inflammatory cytokines including IL-1β, TNF-α, IL-17 and IL-8 in serum in experimental rats. Results demonstrated that triptolide treatment reduced the expression of angiogenic activators Vascular Endothelial Growth Factor (VEGF), Toll-like receptor 2 (Tie2), Angiogenin-1 (Ang-1) and Angiogenin-2 (Ang-2) in synovial cells in experimental rats. Potential mechanism analyses triptolide treatment inhibited expression levels of receptor activator of NF-κB (RANK) ligand (RANKL), which further suppressed RANKL-induced expression and phosphorylation of ERK and AKT at protein levels. Histological analysis showed that triptolide treatment decreased immune cell infiltration and suppressed bone destruction that contributed to attenuation of arthritis severity in CIA rats. In conclusion, these results indicate that triptolide treatment not only inhibits inflammatory cytokines, but also possess anti-angiogenic effect in RA both in vivo and in vitro experiments through down-regulation of RANKL-mediated ERK/AKT signalling pathway, which contributes to understand molecular mechanism mediated by triptolide in the progression of RA.