Heparan sulfate proteoglycan (HSPG) is an integral component of all basement membranes and is implicated in the charge-selective properties of these basement membranes. Studies have shown a decrease in the number of HSPG anionic sites in the retinal capillary and glomerular basement membrane of diabetic animals. This study examined whether a decrease in both HSPG synthesis and its expression as perlecan are reduced in the retina of streptozotocin-diabetic rats. Diabetes was induced in male Wistar rats by intra-peritoneal injection of streptozotocin and the rats were sacrificed 20 weeks later. Retinas were isolated and HSPG synthesis was assessed by incorporation of 35 S-sulfate into heparan sulfate. The expression of mRNA for perlecan was quantified by RNase protection assay. Both the synthesis of HSPG and mRNA expression for perlecan were decreased in the retina of diabetic compared to normal rats. The decrease in HSPG synthesis may account for the reported decrease in retinal basement membrane anionic sites and increased capillary permeability that occurs in diabetes.