Objective To observe the toxic effects of intravitreal injection of etoposide on retinal ganglion cells (RGC) in rabbit eyes. Methods Twenty-four healthy rabbits were divided into 8 groups randomly, including one normal group without any treatment, and 7 experimental groups with intravitreal injection of different dosages of etoposide (0.0, 1.5, 15.0, 150.0, 375.0, 750.0, 1500.0 mu;g).Twelve days after the injection, the animals were killed by air embolism, and the eyeballs were prepared for routine pathological examination with hematoxylineosin staining and transmission electron microscopy. Results Four experimental groups (0.0, 1.5, 15.0, 150.0 mu;g etoposide) had normal retinal structure and normal shape of ganglion cells while other 3 experimental groups with higher dosage of etoposide (375.0, 750.0 and 1500.0 mu;g) showed thinner and disorganized retina. The number of RGC of the normal group and 0.0, 1.5, 15.0, 150.0, 375.0, 750.0, 1500.0 mu;ggroups were 61.66plusmn;3.72, 61.83plusmn;4.59, 60.00plusmn;7.07, 62.00plusmn;4.43, 62.67plusmn;3.98, 7.33plusmn;1.37, 0.00 and 0.00 per 400times;visual field, with statistical difference among groups （F=145.04，P=0.00）. There was no statistical difference between the normal group and 0.0, 1.5, 15.0, 150.0 mu;g groups （F=0.244，P＞0.05）. The number of RGC of 375.0 mu;g group was decreased obviously compared with normal group and 0.0, 1.5, 15.0, 150.0 mu;g groups with statistical difference（F=145.04，P＜0.05）. Conclusion Etoposide has a dosage-dependent toxicity on rabbit RGCs.