Calcification and inflammation are among the important cases of exudative age-related macular degeneration (E-ARMD). The aim of the present study was to elucidate if there is any relationship between serum Osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (RANK-ligand) and E-ARMD. In a cross-sectional study, we compared 45 E-ARMD patients with 45 matched controls. Diagnosis was confirmed by fluorescein angiography. Serum samples were analyzed for OPG, RANK-ligand, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG). The levels of OPG and RANK-ligand were measured by ELISA methods. The mean age was 72.0±11.5 years in the E-ARMD group and 68.2±8.9 years in the control group (p=0.09). The level of serum OPG was 132.10±75.49 pg/ml in the E-ARMD group and 94.88±61.65 pg/ml in the control subjects. E-ARMD patients had significantly high levels of OPG (p=0.012), as well as significantly high levels of LDL-C and TC (p=0.001 and p=0.005, respectively). We could not find any significant difference in RANK-ligand, HDL-C, or TG between two study groups (p>0.05). To the best of our knowledge, this is the first study investigating the levels of OPG in E-ARMD patients. The present study showed that E-ARMD patients had high levels of serum OPG. It may act as a protective factor for E-ARMD or only as a secondary phenomenon of different processes of E-ARMD. Further prospective studies would be necessary for prognostic and predictive significance of OPG in patients affected by E-ARMD.