This study was performed to explore the interaction between chronic neural degeneration and the subsequent vascular remodeling. Weekly urethan administration in rats from birth produces a retinopathy model characterized by photoreceptor degeneration, retinal vascular regression, and retinal pigment epithelium (RPE) neovascularization. We investigated the hypothesis that altered oxygen distribution across the retina and choroid could be involved in the vascular changes seen in this retinopathy. We compared measurements of vitreal, intraretinal, and choroidal oxygen tension (PO₂) distribution in anesthetized and ventilated control and urethan-treated rats at 8 and 16 wk of age with the use of oxygen-sensitive microelectrodes. Striking differences were observed in both choroidal and intraretinal PO₂ distribution in urethan-treated rats compared with controls. At both ages, intrachoroidal PO₂ was much lower in the urethan-treated rats. In addition, the intraretinal PO₂ distribution across the inner retinal layers was more uniform than normal. A small elevation in PO₂ was present at 8 wk in the inner nuclear layer where subsequent vascular regression occurred, and a small reduction in PO₂ was present at the RPE, which recovered to normal values by 16 wk in regions where RPE vessel networks were first evident. Although the retinal arteries were considerably thinner at both ages in the urethan-treated rats, the vitreal PO₂ profiles and superficial retinal PO₂ remained normal. The unexpected and large reduction in the oxygen delivery from the choroid found in the urethan-treated rats may account for the lack of major hyperoxia within the pathological retina and the lower oxygen tension in the RPE before the vascular proliferation in this region. We propose that tissue PO₂ is an important determinant of the vascular remodeling, which is seen in this model of neural degeneration and that the PO₂ distribution changes described in this study help provide a new view of the pathogenesis of this model.