Objective To observe the therapeutic effects of ganciclovir (GCV) with different injection methods on experimental acute retinal necrosis (ARN). Methods The right eyes of 41 pigmented rabbits were infected by herpes simplex virus (HSV-1) (COS strain) to establish ARN animal model. After 24 and 72 hours, GCV was given by intravitreal injection (10 eyes), intravenous injection (11 eyes) and the intravitreal+intravenous injection (10 eyes); intravitreal injection of GCV and dexamethasone (6 eyes) was also included. Four eyes were not treated as the control. The dosage of GCV in intravitreal and intravenous injection was 800mu;g and 5mg/kg weight, respectively. Retina necrosis was observed and the grade was recorded 1-21 days after injection according to the grade standard of retinopathy. The maximum grades of retinal necrosis in different groups were compared. Results The grade of retinal necosis was 3.8 in the control group, and 0.2, 0.4, 0.8, and 2.2 in intravitreal injection, intravitreal+intravenous injection, intravitreal injection with GCV and dexamethasone, and intravenous injection, respectively, 24 hours after the model was set up. The effects of the first 3 groups were obviously better than the last group (P=0.003, 0.011, 0.045); while the difference among the first 3 groups were not significant (P=0.881、0.054、0.107). Seventy-two hours after the model was set up, the grades of retinal necrosis were above 1.4 in 4 groups, and the differences among the 4 groups were not apparent (P=0.214). Conclusions In the animal model of ARN, intravitreal injection with GCV can effectively decrease the grade of retinal necrosis. The difference among intravitreal injection, intravitreal+intravenous injection, intravitreal injection with GCV and dexamethasone, and intravenous injection is not significant.