OBJECTIVES: Retinopathy of prematurity (ROP) is one of the major cause of vision loss among children. Recently, the prevalence of ROP is markedly increasing as the survival rate of very-low-birth-weight premature infants has been improved. It is widely accepted that retinal hypoxia results in the release of factors influencing new blood vessel growth. But, it is little known about the morphological changes of retinal astrocytes and Muller cells in the ROP model. So, we planned to investigate the morphological changes of those retinal glial cells induced by alternating hyperoxic and hypoxic injury in ROP. METHODS: Newborn rats (postnatal day 6) were exposed to two different oxygen concentrations alternating every 24 hours until postnatal day 14. Used oxygen concentrations were 10~15% for hypoxic episode and 55~80% for hyperoxic episode. Afterthen, they were returned to room air. A group of animal served as a room air control. Retinal vascularity was assessed by ADPase reaction and morphology of retinal glial cells was observed using transmisson electron microscope. RESULTS: Preretinal neovascular tufts were observed in 2 out of 12 animals of group III (75/10%) and 4 out of 12 animals of group IV (80/10%), respectively. There was no remarkable structural change of astrocytes. But we could observe some morphological changes of Muller cells. Retraction of the radial processes of Muller cells and breaking of basal lamina were noted at the site of preretinal neovascularization. Decrease in the space occupied by the cytoplasmic processes of Muller cells was observed in the inner nuclear layer of group IV retinae. Infiltration of microglia or macrophage into the vitreo-retinal interface and the site of extravasation was noted. Findings suggestive of neuronal cell death were also observed especially in the inner nuclear layer. CONCLUSIONS: Morphological change of Muller cells and resultant loss of integrity of internal limiting membrane seemed to be the most important step for preretinal neovascularization. But, no structural changes of astrocytes were noted.