[Objective] To explore the role and potential mechanism of human umbilical cord mesenchymal stem cell-exosomes (hUC- MSC-exos) in the prevention and treatment of steroid-induced femoral head necrosis in rats. [Methods] A total of 36 7-week-old male Sprague-Dawley rats were randomly divided into 3 groups, with 12 rats in each group. The animals in the blank control group were given 0.9% normal saline intravenously, those in the model group was given lipopolysaccharide (LPS) and methylprednisolone (MPS) intravenous- ly to create the femoral head necrosis model, while those in the exosome group received hUCMSC-Exos intravenously on the basis of the drugs given in the model group. The rats were sacrificed 28 days later, and the femoral heads were harvested for histological observation and micro CT examination. [Results] Transmission electron microscopy and Western blot showed that the extracts isolated was consistent with the basic characteristics of exos. The empty rate of bone lacunae in three groups showed by HE staining was ranked up-down in order of the model group ＞ the exosome group ＞ the blank control group, with statistically significant differences between them (P＜0.05). Apopto- sis rate of osteoblasts revealed by Tunel staining was also ranged up-down as the model group ＞ the exosome group ＞ the blank control group, which were statistically significant between them (P＜0.05). Compared with the blank control group, the BV/TV, Tb.Th and Tb.N sig- nificantly decreased (P＜0.05), while Tb.Sp significantly increased in the model group (P＜0.05). Compared with the model group, the BV/ TV, Tb.Th and Tb.N significantly increased (P＜0.05), while Tb.Sp significantly decreased in the exosome group (P＜0.05). [Conclusion] The exosomes obtained from human umbilical cord mesenchymal stem cells does prevent steroid-induced femoral head necrosis in rats by inhibiting osteoblast apoptosis in this study.