AIM: To investigate serum levels of soluble CD146 (sCD146) and vascular endothelial growth factor receptor 2 (VEGFR2) in patients with age-related macular degeneration (AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex- and age-matched healthy controls were enrolled in this study conducted in China. Serum samples was obtained from the patients with exudative AMD and from the controls. Serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent assay. RESULTS: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls (t=3.859, P<0.001 and t=3.829, P<0.001, respectively). Serum sCD146 levels were significantly higher in patients with classic choroidal neovascularization (CNV) than in those with occult CNV (t=9.899, P<0.001). There was a significant difference in the trend for exudative AMD in the highest versus lowest quartile of circulating sCD146 levels (χ2=10.29, P=0.001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.696 for sCD146 (95%CI: 0.601-0.791) with an optimum diagnostic cut-off value of 157.16 ng/mL, a sensitivity of 55.7%, and a specificity of 82.2%. CONCLUSION: The serum sCD146 level increases and may be a biomarker for exudative AMD.