This study determined whether retinal degeneration during diabetes includes retinal neural cell apoptosis. Image analysis of retinal sections from streptozotocin (STZ) diabetic rats after 7.5 months of STZ diabetes identified 22% and 14% reductions in the thickness of the inner plexiform and inner nuclear layers, respectively ( P Ͻ 0.001). The number of surviving ganglion cells was also reduced by 10% compared to controls ( P Ͻ 0.001). In situ end labeling of DNA terminal dUTP nick end labeling (TUNEL) identified a 10-fold increase in the frequency of retinal apoptosis in wholemounted rat retinas after 1, 3, 6, and 12 months of diabetes ( P Ͻ 0.001, P Ͻ 0.001, P Ͻ 0.01, and P Ͻ 0.01, respectively).