Objective: To evaluate the neuroprotective effect of App 17-mer peptide on the neuroretina in early or prodromal diabetic retinopathy (DR). Methods: Male Witar rats were injected intraperitoneally with STZ to induce diabetes. Two weeks after the model was created, App 17-mer peptide was injected subcutaneously. One month later, the rats were killed and the retinas were removed for electron microscopic observation of pathologic changes in the neuroretina of diabetic rats and those were treated with App 17-mer peptide. Results: 1 Diabetic rat group: in comparison with control group, showed no pathologic changes in the rod and cone cell layer, the outer nuclear layer, the basement membrane and perivascular cells. However, from neurofibric layer to inner nuclear layer, swelling and deformity of mitochondria were observed with shortening and disappearance of cristae. Medullary degeneration of mitochondria were also seen. There were dark cells in the ganglionic layer. Obvious edema of cell tuber were seen in neurofibric layer and inner plexiform layer. The microvelssels were stenosic and closed because of obvious edema of cell tuber in neurofibric layer. 2 App 17-mer peptide group: In comparison with model group, all the pathologic changes from inner nuclear layer to neurofibric layer were reduced, and mithochondria degeneration was less common. The microvessel stenosis and occlusion disappeared due to decreased cell edema. There was no dark cells in ganglionic layer. Conclusion: 1 During the progression of DR, the pathologic changes of ultrastructure of retinal neuron precede that of microvessle. 2 In the early stage, the injury of retinal neuron may play a role in the mechanism DR. In the early or prodromal stage,timely reversal or reduction of the retinal neuron damage may prevent the onset and progression of DR. 3 App 17-mer peptide may clearly lessen the retinal neuron lesions in DR and is therefore neuroprotective.