Background Osteoporosis (OP) is a common bone disease,which adversely affects life quality.Effective treatments are necessary to combat both the loss and fracture of bone.Recent studies indicated that caffeic acid phenethyl ester (CAPE) is a natural chemical compound from honeybee propolis which is capable of attenuating osteoclastogenesis and bone resorption.Therefore,this study aimed to investigate the effect of CAPE on bone loss in OP mice using micro-computed tomography (CT) and histology.Methods Eighteen mice were prepared and evenly divided into three groups.The six mice in the sham+PBS group did not undergo ovariectomy and were intraperitoneally injected with PBS during the curing period.Twelve mice were ovariectomized (OVX) to induce OP.Six of them in the OVX+CAPE group were intraperitoneally injected with 0.5 mg/kg CAPE twice per week for 4 weeks after ovariectomy.The other six OVX mice in OVX+PBS group were treated with PBS.All the mice were sacrificed 4 weeks after ovariectomy.The tibias were bilaterally excised for micro-CT scan and histological analysis.The Mann-Whitney U test was used to test the statistical differences among groups.Results Bone loss occurred in OVX mice.Compared with the sham+PBS group,mice in the OVX+PBS group exhibited a significant decrease in bone mineral density (BMD,P ＜0.05),bone volume fraction (BV/TV,P ＜0.01),trabecular thickness (Tb.Th,P ＜0.05),and trabecular number (Tb.N,P ＜0.01),as well as a non-insignificant increase in the number of osteoclasts (N.Oc/B.Pm).With CAPE treatment,the microarchitecture of the tibial metaphyses was significantly improved with a reduction of osteoclast formation.Compared with the OVX+PBS group,BV/TV in the OVX+CAPE group was significantly increased by 33.9％ (P ＜0.05).Conclusion CAPE therapy results in the protection of bone loss induced by OVX.