Objective To investigate the neuroprotective effect of hypericin on retinal ganglion cells (RGCs) in a rat optic nerve crush model. Methods Eighteen rats underwent bilateral optic nerve crush. These rats were divided into an untreated group, a saline-treated group, and a hyper- icin-treated group with 6 rats (12 eyes) in each group. Six normal rats acted as controls. 2 % fluoro- gold (FG) was injected into both sides of the superior colliculus to label RGCs retrogradely. The optic nerves were crushed 7 days after labeling. Rats had either no additional treatment or the vitreous cavity was injected with either saline or 5 μl of hypericin. RGCs were counted 14 days later. Re- suits The densities of RGCs decreased sharply 14 days after injury. The survival rate of RGCs in the optic nerve crush groups was 50%, 52% and 68% for the untreated, saline and hypericin-treat- ed groups, respectively. The number of RGCs in the saline-treated group and optic nerve crush group was lower than that in hypericin-treated group. Conclusion Intravitreal injection of hypericin can protect the retinal ganglion cells in a rat optic nerve crush model.