Capillary basement membrane (CBM) thickening is an ultrastructural hallmark in diabetic patients and in animal models of diabetes. However, the wide variety of tissues sampled and diverse methods employed have made the interpretation of thickness data difficult. We showed previously that acellular glomerular BMs in OVE26 transgenic diabetic mice were thickened beyond normal age-related thickening, and in the current study we hypothesized that other microvascular BMs likewise would show increased widths relative to age-matched controls. Accordingly, a series of tissues, including skeletal and cardiac muscle, ocular retina and choriod, peripheral nerve, lung, pancreas, and renal glomerulus was collected from 300 -350-day-old normal and transgenic mice. Transmission electron micrographs of cross sections through capillary walls were prepared, and CBM thickness (CBMT) was determined by the "orthogonal intercept" method. Morphometric analyses showed highly variable transgene-related BMT increases in the sampled tissues, with glomerular BM showing by far the greatest increase (ϩ87%). Significant thickness increases were also seen in the retina, pulmonary alveolus, and thoracoabdominal diaphragm. BMT increases were not universal; however, most were modestly widened, and those that were thickest in controls generally showed the greatest increase. Although the pathogenesis of diabetes-related increases in CBM is poorly understood, data in the current study showed that in OVE26 transgenic mice increased BMT was a frequent concomitant of hyperglycemia. Accordingly, it seems likely that hyperglycemia-induced microvascular damage may be a contributing factor in diabetic BM disease, and that microvessel cellular and extracellular heterogeneity may limit the extent of CBM thickening in diverse tissues. Anat Rec Part A 271A: 332-341, 2003. © 2003 Key words: diabetes; basement membrane thickness; electron microscopy; transgenic diabetic mice OVE26 transgenic mice are diabetic as a result of the specific overexpression of calmodulin in pancreatic beta cells (Epstein et al., 1989(Epstein et al., , 1992. Histological studies show that this results in beta cell destruction early in life, and by 30 -55 days of age glucose values exceed 450 mg/dl. At the same time, insulin levels are reduced to 42% of control levels. OVE26 mice are a particularly valuable model of diabetes, because beta cell toxins need not be administered to induce the disease, and the animals can survive well over a year without exogenous insulin administration (probably because of a small amount of residual insulin secretion). Moreover, because both males and females are fertile for several months without insulin therapy, the transgenic line has been maintained continuously for more than 14 years.Several studies have shown that the OVE26 diabetic model is useful for examining chronic complications of diabetes. This was particularly evident in a previous study of the kidney (Carlson et al., 1997) in which transmission electron microscopy (TEM) morphometry sh...