〔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)/chemokine 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 ovarian 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 applied to detect the number of mature follicles, developing follicles, and blocked follicles in the ovary. Flow cytometry was applied to detect the proportion of BMSCs in the ovaries. QRT-PCR was applied to detect the mRNA expression of mesenchymal transition factor(cMET), hepatocyte growth factor(HGF), SDF-1, and CXCR4 in ovarian 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 ovaries were higher, while the serum levels of β-EP, VEGF, ovarian index, the numbers of mature follicles and developing follicles in the ovary, the expression of SDF-1, CXCR4 mRNA and protein were lower in the POF group(P