Non-arteritic anterior ischemic optic neuropathy (NAION) is characterized by the progressive and irreversible death of retinal ganglion cells (RGCs) which is caused by the insufficient blood supply to the optic nerve (ON) head. At present, hormone therapy is used to reduce optic edema, followed by nerve nutrition therapy to protect the ON. However, no surgical or medical therapy has proven to be beneficial consistently in treating NAION. Vincamine is an alkaloid extracted from the Apocynaceae Vinca plant. Vincamine and its derivatives acting as cerebral vasodilators can easily cross the blood-brain barrier, improve the metabolism of ischemic tissue and protect the neuron. In this study, we aimed to investigate the potential neuroprotection of Vincamine in the photodynamic induced rat model of NAION (rAION), to evaluate its effects and possible mechanisms. We found that Vincamine can rescue RGC death and reduce the number of apoptotic cells. The protection of Vincamine might play through the PI3K/Akt/eNOS signaling pathway. Therefore, Vincamine can be an effective therapy method for NAION.