OBJECTIVE:To investigate the therapeutic effect of Er-Xian decoction (二仙汤,EXD) on the autoim-mune premature ovarian failure (POF) in mice,and its regulatory mechanisms.METHODS:Female BALB mice were treated with a single intraperitoneal injection of zona pellucida 3(ZP3).One week later,mice received low (5 g/kg),moderate (10 g/kg) and high (20g/kg) doses of EXD by gastrogavage once daily for 90 d.Premarin (0.03 mg/kg) served as the positive control group.Serum levels of estradiol (E2),follicle stimulating hormone(FSH) and luteinizing hormone (LH) were measured by enzyme-linked immunosorbent assay,lympho-cyte subtypes were analyzed,and follicular struc-ture differences were observed by hematoxylin and eosin staining.The main mechanisms of POF was in-vestigated by immunohistochemical analysis.RESULTS:Serum E2 levels in POF model mice were decreased,whereas FSH and LH levels were dramat-ically increased.Serum levels of LH and FSH were reduced in POF model mice treated with EXD (mod-erate and high doses) and premarin,while serum level of E2 were increased after POF model mice had been treated with EXD and premarin.The CD3+ T,CD4+ T,CD4+ T/CD8+ T ratio of mice in the positive control group and high and medium dose groups of EXD increased (P < 0.05),and the number of CD8 + T cells decreased significantly (P < 0.05)when compared with the model group.Bone mor-phogenetic protein 15 (BMP15) and Akt were re-pressed in autoimmune POF model mice,whereas high expression was observed in control mice and those treated with EXD (moderate and high doses)and premarin.CONCLUSION:EXD is effective in treating ZP3-in-duced POF in mice and increased expression of BMP-15,and Akt is represented in the mechanism accounting for this therapeutic effect.