This study reports Müller cell and neuronal changes and microglial reaction in streptozotocin-induced diabetic rats. Glial fibrillary acidic protein (GFAP) immunoreactivity was largely confined to astrocytes in the nerve fiber layer (NFL) and ganglion cell layer (GCL) in control rats. In diabetic rats especially those killed after 12 months, GFAP immunostaining could be traced along the entire length of Müller cell processes, extending from the inner to the outer limiting membrane. With the antibody neuronal nuclei, immunopositive cells were located in the GCL and the inner part of the inner nuclear layer (INL) in both diabetic and age-matched control rats. In diabetic rats, labelled cells were reduced in both layers being more marked in the INL. In age-matched control rats, OX42-immunoreactive microglial cells were distributed mainly in the NFL and GCL; some cells were localized in the inner plexiform layer, but rarely in the outer plexiform layer (OPL). Beginning 1 month after diabetes, the microglial cells appeared hypertrophic. Furthermore, microglial number as estimated from cell counts in different layers of the retina was significantly increased, with the occurrence of some cells in the OPL at 4 months. At 14 and 16 months, reactive microglial cells were detected in the outer nuclear layer and photoreceptor layer. Present results suggest that microglial reaction in induced diabetes was elicited by neuronal cell loss in both GCL and INL as well as by some pathologic changes affecting the photoreceptors.