Purpose:　Lacrimal　gland　benign　lymphoepithelial　lesion　(LGBLEL)　is　an　IgG4related　disease　of　unknown　etiology　with　a　risk　for　malignant　transformation.　Estrogen　is　considered　to　be　related　to　LGBLEL　onset.　Methods:　Seventy-eight　LGBLEL　and　13　control　clinical　samples　were　collected　and　studied　to　determine　the　relationship　between　estrogen　and　its　receptors　and　LGBLEL　development.　Results:　The　serological　analysis　revealed　no　significant　differences　in　the　levels　of　three　estrogens　be-tween　the　LGBLEL　and　control　groups.　However,　immunohistochemical　analyses　indicated　that　the　expression　levels　of　ERb　and　its　downstream　receptor　RERG　were　relatively　lower　in　LGBLEL　samples　than　in　control　samples,　with　higher　expression　in　the　lacrimal　gland　and　lower　expression　in　the　lymphocyte　infiltration　region.　However,　low　expression　of　ER　a　was　detected.　The　transcriptome　sequence　analysis　revealed　upregulated　genes　associated　with　LGBLEL　enriched　in　lymphocyte　proliferation　and　activation　function;　downregulated　genes　were　enriched　in　epithelial　and　vascular　proliferation　functions.　The　key　genes　and　gene　networks　were　further　analyzed.　Interactions　between　B　cells　and　epithelial　cells　were　analyzed　due　to　the　identified　involvement　of　leukocyte　subsets　and　epithelial　cells.　B　cell　proliferation　was　found　to　potentially　contribute　to　lacrimal　gland　apoptosis.　Conclusion:　Therefore,　the　tissue-heterogeneous　expression　pattern　of　ER　b　is　potentially　related　to　the　clinical　manifestations　and　progression　of　LGBLEL,　although　further　investigations　are　required　to　confirm　this　finding.