To investigate the neuroprotective effect of melatonin (MT) on retinal ganglion cells (RGCs) in rats with ischemia reperfusion injury (RIR), 24 healthy SD rats were randomly divided into two groups:group A and group B. RIR model was induced in the left eyes by increasing the pressure of the anterior chamber. Group A was treated with 10 % alcohol- normal saline (1 mL/kg/d, ip), while group B was treated with 0.5 % MT (1 mL/kg/d, ip). On the basis of the time interval between the left eyes RIR and the sacrifice, rats in both group A and group B were further divided into 3 subgroups: groups A1 and B1 (days 7), groups A2 and B2 (days 14), groups A3 and B3 (days 30), with4 rats in each subgroup. 7 day before the sacrifice, 3 % fluorogold was bilaterally injected into superior colliculi and geniculate body. The eyes were enucleated after being sacrificed, and mounting of the retina from both eyes was performed on a slide and observed under a fluorescence microscope. Four photos were taken from each of the four quadrants of the retina.The labeled-RGCs were counted by using a computerized image analyzer. The rate of the labeledRGCs was used for statistical analysis. Our results showed that, in group A, the rate of the labeled-RGCs was (77. 16±6.35) %, (65.53±7.01) %, (53.85±4.38) % on day 7, 14 and 30.In group B, the rate of the labeled-RGCs was (81.33±9.27) %, (79.80±8.36) %, (80.34±11.05) % on day 7, 14 and 30. In group B, which was treated with MT after RIR, the rate of labeled-RGCs was significantly higher than that of group A on day 14 and day 30 (P＜0.05). It is concluded that, in the RIR rats, MT therapy could increase the survival rate of the RGCs and could rescue and restore the injured RGCs.