Objective To observe the effectiveness of probucol for non-proliferative diabetic retinopathy (NPDR) with hyperlipidemia. Methods Fifty-two patients (104 eyes) of NPDR with hyperlipidemia were enrolled in this study. The patients were randomly divided into treatment group and control group, 26 patients (52 eyes) in each group. Both groups received diet and exercise guidance, oral hypoglycemic agents and (or) intensive insulin therapy. After blood sugar and blood pressure were controlled, the treatment group received probucol 0.5 g, two times per day; and the control group received atorvastatin of 10 mg, one time per day. The total course was 12 months. Before and after one, three, six and 12 months, all patients underwent vision, ophthalmoscope, fundus fluorescein angiography, blood and urine tested. Variations of visual acuity, fundus condition, macular edema, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC) and 8-0HdG were observed before and after treatment. Results The total effective rate of visual prognosis were 44.23% and 40.38% in the treatment group and the control group, the difference had no statistical significacy (Z=-0.335, P＞0.05). Retinal hemorrhages and microaneurysms alleviated after treatment in both groups.The total efficiency of fundus prognosis was 65.38% in the treatment group and 36.54% in the control group, and the difference was statistically significant (Z=-2.973,P＜0.05). Macular edema was in six and five eyes in the treatment group and the control group respectively, which were lower than before treatment, the difference was statistically significant (chi;2=4.833, 4.300;P＜0.05). Between the two groups, the difference was not statistically significant (chi;2=0.102,P＞0.05). Twelve months after treatment, TG, TC and LDLC were decreased in the treatment group (t=15.653, 7.634, 14.871) and control group (t=13.275, 7.415, 13.632), and the difference was statistically significant (P＜0.05). HDLC showed no significant difference than before in the two groups (t=0.584, 0.275;P＞0.05). TG, TC, LDLC and HDLC showed no difference between the two groups (t=1.857, 0.133, 1.671, 0.875;P＞0.05). 8-0HdG decreased gradually during the one, three, six and 12 months in the treatment group (t=7.352,15.581, 27.324, 28.143) and control group (t=6.877, 8.672, 14.671, 14.855) after treatment, and the difference was statistically significant (P＜0.05). In the first month after treatment, 8-0HdG showed no difference between the two groups (t=0.513,P＞0.05). In the 3, 6, and 12 months after treatment, the 8-0HdG was lower in the treatment group than that in the control group, and the difference was statistically significant (t=3.434, 5.917, 5.226;P＜0.05). Conclusion In the treatment of NPDR with hyperlipidemia, probucol can reduce blood lipid, stable visual function and relieve macular edema.