To modify existing experimental models to simulate the typical clinical presentation of human rhegmatogenous retinal detachment (RRD), namely an RD caused by a retinal break, in a phakic eye, with a posterior vitreous detachment (PVD); to model RRD in a species that is anatomically similar to humans; and to characterize the glial cell response to RRD. Mixed-breed pigs underwent vitrectomy, PVD, subretinal injection of viscoelastic, and creation of a break at the apex of the RD. The crystalline lens was not removed. Follow-up was for 0, 1, and 7 days. Tissue was processed for light and electron microscopy. The glial cell response was characterized using antibodies to glial fibrillary acidic protein (GFAP). Of 11 RRDs created in seven pigs, 10 increased in size and 1 decreased. Light and electron microscopy demonstrated typical features of RD. There was constitutive expression of GFAP in astrocytes and Müller cells with increased immunoreactivity from day 1. This study provided a model of RRD that simulates the typical clinical presentation in humans. It used techniques that most vitreoretinal surgeons are familiar with, and an animal that is widely available and anatomically similar to humans. Anatomic success was high, and the glial cell response established comparability with other species.