Abstract: OBJECTIVE To elucidate the reversal effect of cyclic-icaritin(CICT) on prednisolone -induced osteoporosis， and to explore its mechanism of action with BMPs signaling pathway. METHODS Prednisolone-induced osteoporosis model of zebrafish was used. The stained area， cumulative optical density， calcium and phosphorus contents of the skull of zebrafish were observed by fluorescence inverted microscope (×100). qPCR was used to quantitatively detect the expression of Runx 2 and AKP genes. RESULTS Compared with the control group， the cumulative optical density and mineralized area of zebrafish skull significantly decreased (P<0.01)，the Ca and P levels significantly decreased (P<0.01)， the expression of Runx 2 and AKP genes decreased significantly (P<0.01) after incubation with prednisolone (25 μmol/L).After the intervention with different doses of CICT (0.1， 1.0， 10.0 μmol/L)，the cumulative optical density and bone mineralization area of zebrafish skull significantly increased (P<0.01)， and the levels of Ca and P significantly increased (P<0.01). Molecular docking techniques showed that CICT could stably dock with target protein BMPs (BMP-2/BMP-4)， and the docking scores were - 5.49325609 and - 5.99361658， respectively. The expressions of Runx-2 and AKP genes significantly increased (P<0.01). CONCLUSION CICT can reverse glucocorticoid-induced osteoporosis， which plays an anti-osteoporosis role by binding CICT to BMPs protein target and regulating BMPs signaling pathway to promote osteogenic differentiation.