Objective To explore the mechanism of electroacupuncture at "Zusanli" (ST36) and "Sanyinjiao" (SP06) to activate A2A adenosine receptor (A2AR) for reducing joint inflammation and bone erosion in rats with collagen-induced arthritis (CIA) based on p38 mitogen-activated protein kinase (MAPK) signaling pathway. Methods A total of 32 male SD rats were evenly randomized into control, CIA model, methotrexate (MTX)-treated and electroacupuncture-treated groups. The rats in model, MTX-treated and electroacupuncture-treated groups were immunized to replicate the CIA model by twice injection of fetal bovine typeⅡ collagen and Freund's adjuvant mixture. After the model was successfully established, the rats in the MTX-treated group were injected with MTX 2 mg/kg every 7 days for 14 days, and those in the electroacupuncture-treated group were treated with electroacupuncture (2/100 Hz density wave and output current of 2 mA) bilaterally at ST36 and SP06 for 20 min every day for 14 days. The pathological changes of hind foot bone were observed by computed tomography (CT) imaging; the histopathological changes of synovium, cartilage and osteoclasts of the knee joint were observed by hematoxylin-eosin (H-E), safranin O-fast green and tartrate-resistant acid phosphatase (TRAP) staining; the expression of A2AR, p38, phosphorylated p38 (P-p38), nuclear factor κB (NF-κB) and nuclear factor-activated T cell 1 (NFATc1) proteins in the knee synovial tissue was determined by Western blotting; and the peripheral serum interleukin 1β (IL-1β) content was measured by enzyme-linked immunosorbent assay (ELISA). Results Compared with the control group, the bone density of hind foot in the model group was decreased and the spatial structure was disordered; the cartilage of knee joint was obviously damaged and the synovial tissue was hyperplastic; the number of TRAP positive osteoclasts was increased significantly (P<0.01), while the expression of A2AR, p38, P-p38, NF-κB and NFATc1 in the knee synovial tissue was significantly up-regulated (P<0.01); and the peripheral serum IL-1β content was significantly increased (P<0.01). Compared with the model group, the overall structure of hind foot, synovium and cartilage damage of knee joint in the electroacupuncture-treated group and MTX-treated group were significantly improved; the number of TRAP positive osteoclasts was decreased (P<0.01); the expression of A2AR was significantly up-regulated (P<0.01) and expression of p38, P-p38, NF-κB and NFATc1 was significantly down-regulated (all P<0.01); and the serum IL-1β content was greatly reduced (P<0.01). Compared with the MTX-treated group, the number of TRAP positive osteoclasts was increased in the electroacupuncture-treated group (P<0.05); the expression of A2AR protein was down-regulated (P<0.01), the expression of NF-κB and NFATc1 proteins was up-regulated (P<0.05); and there was no significant difference in the expression of total p38 (P>0.05), but the expression of P-p38 was up-regulated (P<0.05). Conclusion Electroacupuncture at ST36 and SP06 can alleviate the joint bone erosion in CIA rats by inhibiting p38 MAPK pathway to reduce the production of osteoclasts after activating A2AR.