〔Abstract〕 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 .