〔Abstract〕 Objective To explore the effect and mechanism of total saponins of astragalus membranaceus combined with bone marrow mesenchymal stem cells (BMSCs) regulating the stromal cell-derived factor-1 (SDF-1) / chemo- kine receptor 4 ( CXCR4) pathway in the treatment of autoimmune premature ovarian failure ( POF) model rats． Methods Rats were randomly divided into POF group，total saponins of astragalus membranaceus group，BMSCs group ，combination group ，combination + SDF-1 / CXCR4 pathway inhibitor ( AMD3100 ) group ，and control group，with 12 rats in each group．Except for the control group，all other groups of rats needed to construct a POF model．After successful modeling，treatment would begin．The drug injected into the tail vein once a week，and the drug injected into the abdominal cavity once a day for 4 weeks．ELISA was applied to detect the levels of anti ovari- an antibodies (AOAB) ，β-endorphin ( β-EP) ，vascular endothelial growth factor (VEGF) ，tumor necrosis factor- α (TNF-α) ，and interferon-γ ( INF-γ) in serum．Changes in ovarian index were detected．HE staining was ap- plied to detect the number of mature follicles，developing follicles，and blocked follicles in the ovary．Flow cytome- try was applied to detect the proportion of BMSCs in the ovaries．QRT-PCR was applied to detect the mRNA ex- pression of mesenchymal transition factor (cMET) ，hepatocyte growth factor (HGF) ，SDF-1，and CXCR4 in ovar- ian tissue．Western blot was applied to detect SDF-1 and CXCR4 proteins in ovarian tissue．Results Compared with the control group，the serum levels of AOAB，TNF-α , INF-γ , and the number of blocked follicles in the ova- ries were higher，while the serum levels of β-EP，VEGF，ovarian index，the numbers of mature follicles and devel- oping follicles in the ovary，the expression of SDF-1，CXCR4 mRNA and protein were lower in the POF group (P < 0. 05) ．Compared with the POF group，the serum levels of AOAB，TNF-α , INF-γ , and the number of blocked follicles in the ovaries were lower，while the serum levels of β-EP，VEGF，ovarian index，the numbers of mature follicles and developing follicles in the ovary，the proportion of BMSCs，the expression of cMET ，HGF，SDF-1， CXCR4 mRNA and SDF-1，CXCR4 protein were higher in the total saponins of astragalus membranaceus group， BMSCs group，and combination group，and the corresponding indicators in the combination group showed the most obvious change trend (P＜0. 05) ．AMD3100 reversed the effect of total saponins of astragalus membranaceus com- bined with BMSCs on POF rats．Conclusion The combination of total saponins of astragalus membranaceus and BMSCs may inhibit inflammation in POF rats，promote follicular development，increase the proportion of BMSCs in the ovaries，and promote their homing by activating the SDF-1 / CXCR4 pathway，thereby improving ovarian func- tion．