In order to define the pathology of cystoid macular edema (CME), 35 human cases with histopathologic features of CME were reviewed. The macular cysts appeared in different layers of the retina in eyes after cataract extraction, retinal vein occlusion, trauma, diabetes mellitus, and accelerated hypertension. The pathologic process varied from transudation, exudation to liquefaction necrosis. The experimental models of lens extraction and talc retinopathy in rhesus monkeys were examined. Disruption of the blood-retinal barrier at the retinal vasculature and retinal pigment epithelium were noted after lens extraction. Cystoid degeneration of the macula was seen in monkeys with talc retinopathy. The possibility that disruption of the blood-retinal barrier and microinfarction play important roles in the formation of the macular cysts is proposed.