AIM:To evaluate the high sensitivity C-reactive protein (hsCRP), Fetuin-A and matrix γ-carboxyglutamate protein (MGP) as the main factors for vascular calcification and inflammation in serum of patients with advanced age-related macular degeneration (ARMD) in comparison to healthy controls.METHODS: The subjects were 40 patients with choroidal neovascularization (CNV) having a mean age of 70.9±9.1y and a matched group of 49 apparently healthy control subjects. The ARMD was diagnosed using a slit-lamp with superfield lens, fundus photography and fluorescein angiography. Measurement of hsCRP was done by nephelometry method. Levels of Fetuin-A and MGP were measured by enzyme-linked immunosorbent assay (ELISA) technique.RESULTS:hsCRP [0.45(0.07-2.63) mg/L vs 0.25(0.03-1.2) mg/L, P=0.02)] and Fetuin-A levels (50.27±5.04 vs 44.99±10.28 ng/mL, P=0.009) were higher in the patients than in the control groups. We could not find significant difference in MGP level between two groups (P=0.08). There was not a significant correlation between MGP with Fetuin-A and hsCRP among the patients (P=0.7, P=0.9 respectively). A significant negative correlation of hsCRP with Fetuin-A was observed in both case and control groups (P=0.004, r=-0.33 and P=0.001, r=-0.54, respectively).CONCLUSION: Although our study shows that serum hsCRP and Fetuin-A is increased in CNV patients as well as negatively correlated with both study groups, their direct role on pathogenesis of ARMD required future studies.