Background:The Muller cell, the major glial cell in the retina, may be important in diabetes. The purpose of this project was to examine the localisation of glutamine synthetase in control and diabetic Muller cells and to determine whether the number of Mdler cells is altered during diabetes. We also examined whether two experimental treatments of diabetes, aminoguanidine and ramipril, ameliorated these changes. Methods: Normal Sprague-Dawley rats rendered diabetic by a single injection of streptozotocin (50 nig/kg) were treated with either aminoguanidine, ramipril or standard water. Following 12 weeks, animals were sacrificed, their eyes removed and the retinae processed for glutaniine synthetase immunocytochemistry. The level of glutaniine synthetase was quantified in control and diabetic animals and the number of Muller cells counted for each of the treatment groups. Results: In all retinae examined, glutamine synthetase labelled Muller cells along their entire cellular extent and endfeet were more intensely labelled. Following 12 weeks of diabetes, there was a small increase in the level of glutamine synthetase labelling in somata and endfeet compared with controls (ANOVA, P < 0.05). The number of Muller cells was increased following 12 weeks of diabetes (ANOVA, P < 0.0001). This effect was ameliorated by treatment with ramipril and aminoguanidine. Conclusions: These data suggest that Muller cells are altered in number following 12 weeks of diabetes. Moreover, the two experimental treatments were beneficial in preventing this change in Muller cells. Further work is required to establish the mechanisms underlying the change to Muller cells during diabetes.