Objective We studied the effect and mechanism of acupoint catgut embedding on rheumatoid arthritis (RA) by regulating the PD-1/ OX40 signaling pathway. Methods Twenty-five SD female rats were treated with complete Freund’ s adjuvant to establish the RA model. Rats were divided into control, model, Leflunomide, acupoint catgut embedding, and acupoint catgut embedding + Leflunomide groups. The degree of inflammation was determined by the arthritis index. Serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels were measured by ELISA. HE staining was used to observe infiltration of synovial inflammatory cells, synovial tissue, fibrous tissue, macrophage proliferation, and angiogenesis. Proportions of PD-1/ OX40 and CD4⁺ CD28⁺cells were determined by flow cytometry. Results Except for the control group, rats in each group had erythema and moderate swelling from the ankle joint to the metatarsal bone or palm joint. After 14 days, the scores of the model group did not change significantly. Scores of inflammatory factors in the catgut embedding + Leflunomide group began to decrease, and those in the acupoint catgut embedding + Leflunomide group decreased the fastest. Serum levels of IL-6 and IL-8 in the model group were significantly increased (P<0. 01), whereas serum levels of IL-6 and IL-8 in Leflunomide, acupoint catgut embedding, and acupoint catgut embedding + Leflunomide groups were significantly decreased (P<0. 01). The synovial tissue of model group rats was damaged with a large amount of inflammatory cell infiltration, vascular dilation, and fibrous cell proliferation. After treatment with leflunomide and acupoint catgut embedding, inflammatory cell infiltration in synovial tissue was significantly reduced and vascular proliferation was inhibited. The effect was most significant when leflunomide and acupoint catgut embedding were combined. In the model group, PD-1 expression was increased, while OX40 expression was significantly reduced (P<0. 01). CD4 and CD28 expression was significantly increased (P<0. 01). OX40 expression was significantly increased in Leflunomide, acupoint catgut embedding, and acupoint catgut embedding + Leflunomide groups, while CD4, CD28, and PD-1 expression was significantly decreased (P<0. 01). Conclusions Acupoint catgut embedding improves RA symptoms and has a combined therapeutic effect with leflunomide. Its mechanism may be related to the PD-1/ OX40 signaling pathway.