Sugar cataract formation has been demonstrated to result from lenticular sorbitol accumulation. In the lens, the activity of aldose reductase has been observed to increase with the onset of diabetes, while the activity of sorbitol dehydrogenase decreases. This shift in activities of these two Sorbitol Pathway enzymes favors the increased accumulation of sorbitol. Immunohistochemical studies with antibodies prepared against purified rat lens aldose reductase reveal a striking increase in immunoreactive positive staining for aldose reductase in lenses from diabetic rats. Two weeks after the onset of diabetes, increased immunohistochemical staining for aldose reductase appears beneath the epithelial region where water cleft formation occurs, and the intensity of this staining increases with the formation of vacuoles. By 6-8 weeks, the presence of large vacuoles and areas of liquifaction containing dense immunoreactive stain can be observed. Examination of human cataractous lenses with antibodies prepared against purified human placenta aldose reductase suggest similar increases in immunoreactive staining in the human diabetic lens. Cataractous lenses from diabetic patients revealed increased immunoreactive staining for aldose reductase, which was associated with the presence of vacuoles in both the anterior or posterior superficial cortical layers. Examination of similar vacuole containing regions from non-diabetic cataractous lenses revealed no increase in immunoreactive staining for aldose reductase. These results suggest that the enhanced activity of aldose reductase observed in diabetes is due to an increased amount of enzyme, rather than enzyme activation.