OBJECTIVE To develop an in vivo rabbit model of retinal pigment epithelial wound healing that preserves the overlying retina. METHODS Hydraulic débridement of the retinal pigment epithelium was performed in one eye of 35 pigmented rabbits by means of a pars plana vitrectomy approach. Five of the 35 eyes were examined by stereoscopic color fundus photography, fluorescein angiography, and light microscopy on each of the following postoperative days: 0, 2, 4, 7, 14, 28, and 56. RESULTS Retinal pigment epithelial débridement with this technique results in apical decapitation of the retinal pigment epithelial cells followed by subsequent hydraulic removal of the residual nucleus-containing basal cellular debris. The retinal pigment epithelium-denuded Bruch's membrane was resurfaced mostly by a monolayer of flattened, hypopigmented retinal pigment epithelial cells within 4 days after débridement. Progressive retinal pigment epithelial hyperplasia also occurred beginning between postoperative days 2 and 4. CONCLUSIONS Retinal pigment epithelial wound healing after hydraulic débridement occurs rapidly and in a manner initially consistent with sliding migration. Progressive retinal pigment epithelial hyperplasia also occurs and may contribute to this repair process. Further investigation of retinal pigment epithelial repair by means of this in vivo model may provide important insight into the pathogenesis and treatment of outer retinal disorders.