Objective To explore the alterations of estrogen and its receptors in peripheral venous blood of postmenopausal patients with primary Sjgren's syndrome (pSS) and their possible roles. Methods The clinical data and laboratory test indexes of 60 postmenopausal pSS patients and 60 postmenopausal healthy subjects were collected, and fasting peripheral venous blood was collected. The plasma E2 level of the two groups was detected by enzyme-linked immunosorbent assay. The mRNA expression levels of ERα, ERβ and GPR30 in peripheral blood mononuclear cells of the two groups were detected by real-time fluorescent quantitative polymerase chain reaction. The protein expression levels of ERα, ERβ and GPR30 in PBMCs of the two groups were detected by Western blot. SPSS17.0 statistical software was used to analyze the data. Rank sum test and t test were used to compare the measurement data between groups, and Spearman correlation analysis was used to analyze the correlation between variables. Results The mean level of plasma E2 in pSS group was lower than that in HC group (P＜0.01). ERα and ERβ mRNA in pSS group were significantly lower than those in HC group (P＜0.01), while GPR30 mRNA in pSS group was significantly higher than that in HC group (P＜0.01). Spearman correlation analysis found that GPR30 mRNA was positively correlated with GLB in PBMCs of pSS group (r=0.411, P=0.001). There was no significant difference in ERα protein expression level between pSS group and control group (P＞0.05), ERβ protein expression level was significantly lower than that of control group (P＜0.01), but GPR30 protein expression level was significantly higher than that of control group (P＜0.05). Conclusion The differential expression of estrogen and its receptors in peripheral blood of patients with primary Sjogren's syndrome suggests that estrogen and its receptors may be involved in the occurrence and development of pSS