Objective To observe the effect of Etanercept on the expression of Fas, TNF-α, and caspase-8 in the retinal apoptotic pathway in diabetic rats, and to explore the therapeutic effect of etanercept on diabetic retinopathy. Methods SD rats were randomly divided into control group, model group, and treatment group. A streptozotocin(STZ)diabetic rat model was established. The blood glucose and body weight of the model rats were measured every week. Specimens from each group were obtained after 12 weeks of treatment. The expression of Fas, TNF-α, and caspase-8 in rat retina was quantitatively detected by Western-blot, and Evans blue leakage test was used to compare the quantitative determination of retinal vascular leakage in each group of rats. Result The expression of Fas, TNF-α, and caspase-8 with Western-blot in the treatment group was lower than that inthe model group(P<0.01), while in the treatment group and the model group they were higher than that in the control group(P<0.01). The Evans blue leakage test was used to detect the retinal leakage in each group, and it showed the leakage in the treatment group was lower than that in the model group(P<0.01), while in the treatment group and the model group it were higher than that in the control group(P<0.01), while in the treatment group and the model group it were higher than that in the control group(;0.01). Conclusion Etanercept can effectively reduce the expression of Fas, TNF-α, and caspase-8 in the retinal apoptotic pathway of diabetic rats, and it can reduce the leakage of retinal cells in diabetic rats, effectively reduce the retinopathy of diabetic rats as well.