〔Abstract〕 Objective To explore the effect of cannabinoid receptor 2(CB2) on orthodontic tooth movement(OTM) rate and periodontal tissue reconstruction of pressure area in mice. Methods Thirty CB2-/-male mice and thirty littermate control WT male mice were individually accepted the orthodontic appliance at their age of 6 weeks. The mice were respectively scarified at 3 days, 7 days, 14 days and 21 days after the operation. Then the tooth movement distance was examined through the stereomicroscope. Hematoxylin-eosin staining was performed to explore the biological responses of periodontium at the distal mesial root pressure area. Anti-tartrate acid phosphatase staining was performed to calculate the number and distribution of osteoclasts at the distal mesial root pressure area, and MMP-9 was evaluated by immunohistochemistry to examine the number of MMP-9(+) monocytes and multinucleated cells in the same district as the TRAP staining. Results Compared with those WT mice at 3,7,14 and 21 days, OTM distance showed a gradual increased tendency according with experimental time over 21 days. The widths of periodontal ligament on the pressure side were markedly greater in CB2-/-mice than WT mice at 7,14 and 21 days(P<0.000 1). The numbers of TRAP positive osteoclasts were significantly greater in CB2-/-mice than those in WT mice at 14 days of OTM(P<0.001). MMP-9 immunohistochemical staining showed that the number of MMP-9(+) monocytes and multinucleated cells was more in CB2-/-mice than that in WT mice at 14 days of OTM(P<0.05). Conclusion The absence of CB2 accelerates orthodontic tooth movement under orthodontic force. The absence of CB2 reinforces bone resorption in orthodontic tooth movement compressive area during orthodontic tooth movement.