This study investigated the reactive changes in Muller glial cells and astrocytes of the rat retinae, which had been subjected either to hypoxia or to hypoxia followed by hyperoxia treatments. Fifteen rats were used. Ten rats were exposed to 9% O-2 for 2 h. Of these, five rats were killed at 24 h later; the remaining five rats were immediately exposed to 80% O-2 for 2 h and then killed 24 h later. Double immunofluorescence was carried out between nestin and glutamine synthetase (GS) and between glial fibrilary acidic proteins (GFAP) and GS in normal and pathological retinae. Enhanced nestin expression was observed in reactive astrocytes following hypoxia treatment as revealed in whole mount sections. A novel finding was the induction of nestin expression in Muller glial cells. Remarkably, the nestin immuno-staining was downregulated to levels comparable to those of the normal rats with immediate hyperoxia treatment. Induced nestin expression by hypoxia colabelled with GFAP in astrocytes, however, remained unaffected after hyperoxia treatment. The induced expression of nestin in Muller glial cells and astrocytes in hypoxia and differential downregulation after hyperoxia treatment suggest a structural plasticity of the cytoskeletal framework of these cells. The differential response after hyperoxia treatment may be related to the functional states of the cells.