Objective To observe dynamically the response of the retinal ganglion cells (RGCs) following chronic optic nerve compression in cats. Methods Thirty adult cats were randomly divided into 6 groups (n=5): normal control group, sham operation group, 1-week compression group, 2-week compression group, 4-week compression group and 8-week compression group. The chronic optic nerve injury was produced by an inflatable balloon implanted under the optic chiasm. RGCs of all animals were labeled with Dil by retrograde tracing 2 weeks before operation. After each group animals were killed by perfusion, the retina were harvested to observe the pathological changes using the light microscope and electron microscope and the number of RGCs was counted under fluorescence microscope. Results There were three cell layers in normal HE stained retinas of cats with clear limits, named ganglion cell layer, bipolar cell layer and photoreceptor cell layer in sequence from vitreous body to selera. By 4 weeks after optic nerve compression, there were no obvious pathological changes in the retinas, however, at 8 weeks the nuclei of the RGCs became markedly thin, with the larger almost disappearing, and the total thickness of the retinas reduced with the glial cells proliferating. Under electron microscopy, the RGCs of the normal eats had large ovate nuclei with homogeneous karyoplasms. The cytoplasm occupied only small space of the cells, but contained a great of cellular organelle. At 4 and 8 weeks after compression, it was found in the retinal ganglion cells that the components of cytoplasm reduced, the endoplasmic reticulum expanded, the mitochondria was swollen, the vacuole occurred under the plasma membrane, the membrane of nuclei was shrunk and the chromatin was marginated and condensed. The density of the DiI labeled RGCs in the normal group animals ranged from 406 to 527 cells/mm2, with an average of (465±38) cells/mm2 and higher density in the central area than in the peripheral one. The number of the RC, Cs was unchanged by 4 weeks after optic nerve compression, but 8 weeks later, the number declined significantly to (293±32) cells/mm2 by about 37%. Conclusion The RGCs present delayed and secondary degeneration following chronic optic nerve compression, which gives an opportunity to protect the RGCs.