Perfluoropropane (C3F8) was injected into nine eyes of six cynomolgus monkeys. In all nine eyes, macular changes consistent with the development of a macular cyst were noted within 3 months after injection. On fluorescein angiography, there was no evidence of retinal vascular leakage associated with the macular cysts. Histopathologic evaluation of six eyes demonstrated microcystic changes throughout the perifoveal inner nuclear layer. These coalesced into larger cystic spaces in the outer plexiform layer of the central macula. These macular changes are previously unreported in patients or monkeys undergoing intravitreal injection of expansile gases. This model for macular cysts may be helpful in evaluating the pathogenesis and role of interventional strategies in patients with cystoid macular edema.