The most characteristic findings of diabetic background retinopathy in humans are increased capillary permeability and progressive vascular occlusions. According to studies correlating angiographic in vivo findings with post-mortem retinal digests microaneurysms cluster around areas of capillary non-perfusion [1,2], possibly in an early abortive attempt at retinal new vessel formation. From earlier work it is known that pericytes may disappear leaving behind empty pockets in the capillary basement membrane [3]. Since endothelial cells do not leave behind such traces when they disappear, their fate during the initial course of retinal damage is uncertain, despite indication for both focal loss, leading to acellular capillaries, and focal proliferations leading to hypercellular vessels and microaneurysms [4,5]. Pericyte loss and acellular, occluded capillaries have been found in diabetic animals, in which the natural course of diabetic retinopathy has been studied [6,7]. Diabetologia (1998) Summary To assess the relationship between glucose and advanced glycation end products (AGE) and the relationship between AGE and retinal changes in vivo, we studied the time course of retinopathy over 12 months in trypsin digest preparations and measured glycaemia and retinal AGE in spontaneous diabetic hamsters of mild (MD) and severe (SD) phenotypes. Blood glucose levels were elevated in MD (9.44 ± 0.76 mmol/l) and in SD (3 months: 24.3 ± 1.4 mmol/l; 12 months: 31.7 ± 0.8 mmol/l) over nondiabetic controls (NC: 7.15 ± 0.25 mmol/l; p < 0.05 or less vs MD; p < 0.001 vs SD). Similar relations were found for HbA 1 . Retinal AGE in mild diabetes was 405 ± 11.3 arbitrary units (AU) (NC 245 ± 7.7; p < 0.01) after 3 months and remained unchanged. A non-linear increase of AGE over time was found in severe hyperglycaemic hamsters (466 ± 21 AU after 3 months and 758 ± 21 AU after 12 months; p < 0.001 vs MD). Pericyte loss in mild diabetes progressed from ±26 % after 3 months to ±41 % after 12 months (p < 0.001 vs NC). Whereas the initial pericyte loss in severely diabetic hamsters was identical to the mildly diabetic group, a higher degree of pericyte loss occurred after 12 months (±57 %; p < 0.05 vs MD). Endothelial cell numbers remained unaffected by mild hyperglycaemia, but significantly increased over time in severe diabetes reaching 31.7 % above controls after 12 months (p < 0.001 vs NC and MD). Microaneurysms were absent in all retinae examined. Acellular capillary segments were increased in mild diabetes (3.83 ± 0.31 per mm 2 of retinal area) and severe diabetes (7.83 ± 0.73) over controls (1.0 ± 0.23). These data suggest that a threshold of glycaemia might exist above which AGE removal systems become saturated. Pericyte loss and acellular capillary formation are associated with mild increases in blood glucose and AGE levels while endothelial cell proliferation requires higher glucose and AGE levels. [Diabetologia (1998) 41: 165±170]