Objective To investigate the regulatory effect of adiponectin on RANKL/OPG in peripheral circulation and its therapeutic effect on diabetic osteoporosis.Methods High fat diet combined with streptozomycin was used to construct diabetic osteoporosis model mice,which were treated with adiponectin and alendronate sodium as positive control.They were divided into control group,model group,treatment group and positive control group.After the intervention,the weight of the mice was measured,the venous blood of the mice was collected,and the fasting glucose level,glucose tolerance test,and serum RANKL/OPG were detected.The primary bone marrow mesenchymal stem cells were extracted from the femur of mice in each group,induced osteogenic differentiation and stained with alizarin red to detect the expression levels of Opg and Rankl genes.The lumbar 3 vertebrae of mice were obtained,and the changes of bone microstructure in each group were detected.Results After adiponectin treatment,compared with the model group,the body weight,fasting blood glucose level and glucose tolerance test were significantly decreased,serum OPG concentration increased,serum RANKL concentration decreased,and serum RANKL/OPG decreased in the treatment group.Compared with the control group,the bone formation ability of bone marrow mesenchymal stem cells in the model group was significantly weakened,and RANKL/OPG was significantly up-regulated.Compared with the model group,the osteoblastic differentiation ability of bone marrow mesenchymal stem cells in the treatment group was significantly enhanced,and RANKL/OPG was significantly down-regulated.After adiponectin treatment,the number of osteoblasts per unit length,the percentage of trabecular area and the thickness of trabecular were significantly increased.Conclusion Adiponectin can reduce the body weight of diabetic mice,reduce fasting blood glucose,partially restore the body's blood glucose regulation ability,up-regulate Opg gene expression and inhibit Rankl gene expression,promote bone marrow mesenchymal stem cell osteogenic differentiation,and improve bone microstructure,which is a potential choice for the treatment of diabetic osteoporosis.