Purpose: The purpose of present study is to characterize the Idiopathic epiretinal membrane (iERM) through phosphoproteomics to facilitate its diagnosis and treatment. Experimental design: The vitreous of 25 patients with iERM and 15 patients with idiopathic macular hole were analyzed by proteomic and phosphoproteomic analysis based on tandem mass tag. PRM was used to verify differential proteins. Results: Proteomic analysis identified a total of 878 proteins, including 50 differential proteins. Phosphoproteomic analysis identified a total of 401 phosphorylation sites on 213 proteins, including 27 differential phosphorylation sites on 24 proteins. Twenty six proteins of these differential proteins and phosphorylated proteins may be closely related to fibrosis in iERM. MAPKAPK3 and MAPKAPK5 are predicted as the major kinases in vitreous of iERM. Conclusion and clinical relevance: Our results screened candidate proteins for the treatment of fibrosis in iERM, among which tenascin-C, galectin-3-binding protein, glucose-6-phosphate isomerase, neuroserpin, collagen alpha-1(XI) chain and collagen alpha-1(II) chain are expected to become potential biomarkers or therapeutic targets for iERM. In addition, this article expand the data of vitreous phosphoproteome, and provide a reference resource and new enlightenment for studying the pathogenic mechanisms of retinal diseases.