Abstract: Rheumatoid arthritis (RA) is a disease that seriously affects human health, and the existing treatments have the disadvantages of high side effects, drug resistance and poor effectiveness. In this study, we proposed a new anti-RA strategy based on the cross-linked hydrogel "acupuncture + swelling" dual stimulation of acupoints, and investigated the efficacy of brucine hydrogel microneedles targeting for RA in mice. All animal experimental procedures were approved by the Guizhou University of Traditional Chinese Medicine Laboratory Animal Ethics Committee (No: 20230179) and conducted in accordance with its guidelines. A mouse model of collagen-induced arthritis (CIA) was established, and the efficacy was investigated by using the swelling of the paw, spleen and thymus indices, histopathological sections of the ankle joints, serum levels of inflammatory factors and synovial tissue proteins, and it was found that the acupoint microneedling group and the acupoint + non-acupoint microneedling group could significantly decrease the swelling of the paw in the mouse model of CIA, reduce the swelling of the immune organs of the mice, reduce the levels of serum inflammatory factors, and improve the efficacy of CIA. Inflammatory factor content, improve the pathological state of synovial membrane and cartilage tissue of ankle joint and down-regulate the expression level of related inflammatory proteins in CIA mice, which has the effect of alleviating rheumatoid arthritis. The therapeutic strategy of brucine hydrogel microneedles based on "acupuncture + swelling" to stimulate the Zusanli (ST36) acupoint can significantly treat rheumatoid arthritis, which provides an important scientific basis for the subsequent development and utilisation of acupoint microneedles transdermal drug delivery system.