The restoration of the outer blood-retinal barrier following krypton laser injury to the rat retina was studied at small and large laser lesions using intravenously injected sodium fluorescein, horseradish peroxidase, and catalase. The regenerated choriocapillaris and new blood vessels were permeable to fluorescein and peroxidase, but not to catalase. The regenerating retinal pigment epithelium gradually reformed a continuous sheet of cells covering all small laser sites and the periphery of large lesions. Zonulae occludens between the regenerated cells restored the outer retinal barrier and prevented diffusion of peroxidase into the retina. This occurred along Bruch’s membrane and the new blood vessels that were covered by the regenerated pigment epithelial cells, but not in the center of the large lesion that was not relined by regenerated cells.