AIM:To investigate the protective effects of soy isoflavones on retinal ganglion cells(RGCs)damage in diabetic rats and related mechanisms.METHODS: Totally 80 male SD rats(80 eyes), aged 4-6 weeks, were randomly divided into four groups(n=20 per group): a control group, a diabetic model group, a low-dose soy isoflavone treatment group, and a high-dose soy isoflavone treatment group. Among them, the control group was fed normal chow, while the diabetic group, soy isoflavone low-dose-treated group, and soy isoflavone high-dose-treated group were fed high-fat chow. After a feeding period of 4 wk, rats in the diabetic group, as well as those in the soy isoflavone low-dose and high-dose treatment groups, were injected intraperitoneally with streptozotocin(STZ)at a dose of 50 mg/kg to establish a diabetic model. Rats in the control group received an equivalent volume of sodium citrate buffer acid. The soy isoflavone low-dose-treated group was administered 360 mg/kg of soy isoflavones daily via gavage, while the soy isoflavone high-dose-treated group received 540 mg/kg of soy isoflavones daily via gavage. Both the control group and the diabetic group were given an equal amount of purified water daily via gavage. Body weight and blood glucose levels were measured at 4 and 8 wk post-gavage treatment. The eyes were extracted and the retinas were dissected at 8 wk following the gavage treatment. The number of RGCs in each group was determined using immunochemical tissue staining and protein blotting techniques, while the superoxide dismutase(SOD)activity and malondialdehyde(MDA)content of the rat retinal tissue were measured through histochemical methods.RESULTS: Compared with diabetic rats, treatment with high-dose soy isoflavones for 8 wk resulted in a reduction of blood glucose to 8.9±1.23 mmol/L, an increase in intraretinal SOD activity to 849.93±63.71 U/mgprot, a decrease in MDA content to 45.77±0.59 nmol/mgprot, and an increase in the number of RGCs to 76±1 cells/mm2, which is comparable to the control group's data(all P<0.05).CONCLUSION: Soy isoflavones can reduce retinal oxidative stress in diabetic rats and protect RGCs.