Endothelial dysfunction underlies many of the complications associated with diabetes. Diabetic retinopathy (DR) is a leading cause of blindness. The final stage of DR, proliferative diabetic retinopathy (PDR), is characterized by the abnormal proliferation of retinal endothelial cells, which form new blood vessels that invade the vitreous humor. Except for hyperglycemia, no other mechanism has been clearly established as the main contributor to the initiation and progress of DR. Our hypothesis is that hyperglycemia interferes with endothelial programs directing vessel regression, contributing to the vascular invasion of the vitreous. Using an in vitro endothelial tube formation assay, we determined that stimulation of bovine retinal endothelial cells (BREC) with growth factors resulted in their organization into tubes. These structures spontaneously regress within a day of their formation. Using this model, we analyzed the effect of diabetes on vascular stability. Addition of vitreous humor from non-angiogenic DR patients to pre-formed tubes resulted in vascular regression, as was observed in specimens with non-diabetic ocular disease. We noted that the addition of vitreous humor from PDR patients delays the regression of BREC derived tubes. These exciting results suggest that to maintain a healthy, vascular vitreous humor, vascular regression pathways are constitutively active. This raises the possibility that the progress to angiogenic PDR requires the inhibition of regression pathways.