Background : A dacryolith mainly contains organic material, but its specific protein content is unknown. We observed a unique dacryolith formation in patients with long-term use of rebamipide eye drops and tried to identify the differences in protein compositions of dacryoliths from patients with or without use of rebamipide eye drops using novel proteomic analysis. Methods: Dacryolith samples were obtained from 7 patients (4 samples were without rebamipide usage, 3 were with rebamipide usage) who underwent endo-dacryocystorhinostomy or lacrimal endoscopic surgery and were subjected to protein identification and metaproteomic analysis. Results: The proteomic analysis revealed that most core proteins of dac-