To investigate the effect of autologous peripheral nerve grafting on retinal ganglion cell survival and axonal regeneration after an injury, the optic nerve of adult Sprague-Dawley rats was transected and grafted with an autologous peripheral nerve from the peroneal branch of the left sciatic nerve. The numbers of both surviving and axon-regenerating retinal ganglion cells were determined at different times after surgery. The majority of retinal ganglion cells were rapidly lost within 3 weeks, followed by a slow and protracted phase of cell loss until the end of the 6-month study. FluoroGold-labelled axon-regenerating retinal ganglion cells were first detected by 2 weeks, followed by a period of high axonal regeneration that peaked at 8 weeks and accounted for over 35% of the total surviving retinal ganglion cells. However, retinal ganglion cells with regenerated axons eventually died. Our data thus indicate that axonal regeneration in the autologous peripheral nerve graft is insufficient to sustain the long-term survival of axotomized retinal ganglion cells.