To examine the expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR)-2 in enucleated eyes with Coats' disease. Formalin-fixed, paraffin-embedded tissue sections from nine globes with Coats' disease were submitted for hematoxylin and eosin staining and immunohistochemistry with anti-VEGF and VEGFR antibodies. Histologically, the enucleated eyes demonstrated the presence of macrophage infiltration and cholesterol clefts in the subretinal space. There were marked retinal vascular abnormalities, including dilated vessels with hyalinized vessel walls in six globes. Exudative retinal detachment was noted in all globes. VEGF immunoreactivity was observed in macrophages infiltrating the subretinal space, and in the detached retina including several blood vessels. VEGF-positivity in macrophages was significantly higher in cases containing retinal vessel abnormalities than those without the abnormalities (P < 0.01). VEGFR-2 immunoreactivity was detected in endothelial cells lining the abnormal retinal vessels, where VEGFR-1 or VEGFR-3 was not expressed. Immunoreactivity for VEGF and VEGFR-2 was detected in macrophages and endothelia of abnormal vessels in eyes with Coats' disease. These results suggest that anti-VEGF approach is a promising therapy for patients with Coats' disease.