OBJECTIVE: to investigate the anti-arthritic effects of lappaconitine (LA) on adjuvant-induced arthritis in Sprague-Dawley rats and its possible involvement in the regulation of M1/M2 macrophage balance through the P2X7 receptor (P2X7r). METHODS: Rats were immunized with complete Freund's adjuvant and then intraperitoneally administered LA (2, 4, or 8 mg·kg RESULTS: LA treatment significantly reduced AI scores, paw swelling, joint destruction, and inflammatory cell infiltration, and alleviated arthritis pain. Additionally, LA promoted a balanced M1/M2 ratio by increasing the mRNA expression level of M2 marker arginase 1 and decreasing those of M1 markers inducible nitric oxide synthase and interleukin (IL)-1β in synovial tissues. Furthermore, LA lowered the levels of three M1-related cytokines, namely tumor necrosis factor-α, IL-1β and IL-18, and raised the level of the M2-related cytokine IL-10. Further research showed that treatment with LA inhibited the expression of P2X7r. CONCLUSION: Our findings indicate that the notable therapeutic and analgesic effects of LA on AIA rats are exerted through balancing the M1/M2 ratio, probably via P2X7r.