The mechanistic target of rapamycin complex 1 (mTORC1) signaling has been reported to regulate lens-induced myopia (LIM) in guinea pigs. To address the challenge of delivering lipophilic mTORC1 inhibitors to the posterior eye segment, we developed a novel topical ophthalmic formulation of everolimus, a second-generation rapamycin derivative available only orally, and evaluated its antimyopic efficacy, ocular pharmacokinetics, and safety.Vehicle formulations were optimized for delivering everolimus to the RPE-choroid complex. The efficacy of different concentrations of everolimus eye drops was tested in 3-week-old male pigmented guinea pigs that underwent LIM. We examined mTORC1 signaling activation, axial elongation, refractive changes, and fundus morphology. Pharmacokinetics was assessed in guinea pigs and New Zealand white rabbits. Ocular safety was evaluated through slit-lamp and fundus examinations, intraocular pressure measurements, and histologic analysis.The optimized formulation of everolimus eye drops (0.001%, 0.01%, and 0.1% w/v) significantly attenuated axial elongation by 0.10 ± 0.03 mm (P = 0.054), 0.11 ± 0.02 mm (P = 0.001), and 0.14 ± 0.03 mm (P = 0.001), respectively. The everolimus eye drops also attenuated fundus tessellation, choroidal thinning, and mTORC1 activation. Peak everolimus concentrations in the RPE-choroid complex of guinea pigs ranged from 5.6 to 103 ng/g, with a Tmax of 1 hour. In rabbits, 0.005% to 0.01% everolimus eye drops achieved concentrations in the RPE-choroid complex comparable to the therapeutic levels in guinea pigs. No corneal, lenticular, retinal toxicity, or intraocular pressure alterations were observed.This novel ophthalmic formulation effectively delivered everolimus to the posterior segment and inhibited myopia progression, supporting its clinical potential for myopia control.