Objective: To detect estrogen receptor α and β(ER-α, ER-β)protein expression in different age of mouse thymus.Methods:Protein expression of ER-α and ER-β in thymus was analyzed via immunohistochemistry.Moreover,the relationship between ER-α and cytokeratin 18(epithelial cell marker)was further tested through fluorescence double-staining.Results: Immunohistochemical analysis revealed that both ER-α and β protein was found in nuclei of some thymocytes of 3 month mice.However,expression of ER-β was absence while ER-α was still positive in aged mice, such as 12 months and 16 months old.Double staining further confirmed that lots of ER-α/β positive cells were Foxp3 negative cells.Conclusion: Expression of ER-β is absent while ER-α is still positive in thymus of aged mice, which indicates ER-α is the critical estrogen receptor that involves in thymic involution.Moreover, ER-α/β do not participate in Treg development within thymus.