Purpose: Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, with chronic pain as its typical symptom. Although studies have shown that an activated peripheral CB2 receptor can reduce acute pain, whether the CB2 receptor is involved in electroacupuncture (EA) inhibiting chronic pain and the involved mechanism remains unclear. The aim of this study was to investigate whether EA may strengthen peripheral CB2 receptor-inhibited chronic pain in a mouse model of KOA. Materials and methods: KOA was induced by intra-articular injection of monosodium iodoacetate (MIA) into the left knee joint of mice. Thermal hyperalgesia was tested with the hot plate test, and mechanical allodynia was quantified using von Frey filaments. The expression of CB2 receptor and IL-1 beta were quantified by using immunofluorescence labeling. Results: EA treatment at 2 Hz+1 mA significantly increased the expression of CB2 receptor in fibroblasts and decreased the expression of IL-1 beta in the menisci compared with that in the KOA group. However, EA had no effect on the expression of IL-1 beta in CB2(-/-) mice. At 2 Hz+1 mA, EA significantly increased mechanical threshold, thermal latency, and weight borne after KOA modeling. However, knockout of the CB2 receptor blocked these effects of EA. After 2 Hz+1 mA treatment, EA significantly reduced the Osteoarthritis Research Society International (OARSI) score after KOA modeling. However, EA had no significant effect on the OARSI score in CB2(-/- )mice. Conclusion: EA reduced the expression of IL-1 beta by activating the CB2 receptor, thus inhibiting the chronic pain in the mouse model of KOA.