The pathoqenesis of diabetic retinopathy has not been fully explained. The earliest histological lesion is the loss of intramural pericytes and thickening of the basement membrane. Increased activity of the polyol pathway is a probable mechanism for these two abnormalities. Investigations have suffered from the lack of an exact animal model simulating the human condition.Examination of the retina in the spontaneously diabetic BB-rat demonstrated degeneration and loss of intramural pericytes, a progressive increase in basement membrane thickness, and microinfarctions with areas of non-perfusion. Therefore, this model may be used to clarify the biochemical mechanism(s) linking the metabolic abnormalities of diabetes and the retinopathy.