Purpose: To evaluate the efficacy of subconjunctival injections of Etoposide for retinoblastoma(RB) mice.Method: Twenty-five RB mice were divided into 5 groups for the study(G0～G4). GO for control group received 0.9% sodium chloride injection subconjunctival. G1: 5 RB mice for systemic delivery received 6 systemic administration of Etoposide 150 μg and Cyclosporin A (CSA)1.0mg at 3 days intervals, respectively. G2～G4:5 RB mice in each group received 6 subconjunctival delivery of Etoposide in 50、75、150μg at 3 days intervals, respectively.To observe the changes of the volume of RB in anterior chamber and the part of conjunctiva for injections of chemotherapeutic drugs. All eyes and conjunctiva and scleras of the part for drugs injections were obtained at 6 weeks after experiment for histopathologic examination. The findings under the light microscope were analysed with software to measure the areas of RB in anterior chambers and the tumor inhibition rate.Results:The volume of RB in anterior chambers for G1 and G2 increase quickly and none of the mice exhibited tumor control. The RB volume increase slowly in G3 and exhibit tumor control in G4. The areas of tumors in G0～G4 are 0.710,0.659,0.634,0.515,0.235 mm2, respectively. The rate for tumor inhibition in G0～G4 are 0.0%,7.18%, 10.70% ,27.43% ,66.90%, respectively. There are statistical significant difference between the G1 and G4 for the volumes of tumors and the rate of tumor inhibition.The pathologic examination of subconjunctiva and sclera for the injective sites showed no pathologic changes.Conclusions: There are significant effects for the method of subconjunctival delivery of Etoposide in RB control, demonstrating a positive dose-related relationship. Subconjunctival injection of Etoposide reached better efficacy in controlling and inhibiting RB cells than systemic delivery of Etoposide for the same dose. The pathologic results showed the subconjunctival delivery of etoposide were safety for conjunctiva and sclera. It would be one of effective and safety method of chemotherapy for RB.