ObjectiveTo observe the effect of phase Ⅱenzyme inducer 5, 6-dihydrocyclopenta 1, 2-dithiole-3-thione (CPDT) on nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signal pathway and oxidative stress in the retina of type 2 diabetic rats. MethodsThirty-five male Wistar rats were randomly divided into two group, normal group and model group. Model group were further randomly divided into two group, diabetic group and CPDT intervention group. There were 8 rats in the normal group and 27 rats in the model group. Diabetic group and CPDT intervention group were given high fat and high sugar diet for 2 months. After 12 hours of fasting, type 2 diabetic rat model was induced by intraperitoneal injection of low dose of streptozotocin. CPDT was added into the high fat and high sugar diets at 1 week after the diabetic model was established in the CPDT intervention group. Eight weeks after CPDT treatment, blood glucose, serum malondialdehyde (MDA), blood lipid, Nrf2 and hemeoxygenase-1 (HO-1) expression were evaluated. ResultsType 2 diabetic model was successfully established in 25 rats, the success rate was 92.6%.The level of blood lipid of diabetic group was higher than those of the normal group (FTC=65.866, FTG=25.441, FLDL-C=38.889; P=0.000). Blood glucose was significant different between all groups (χ2=25.812, P=0.000), and was significantly higher in diabetic group than that in normal group and CPDT intervention group. The serum MDA content was significant different between all groups (F=59.545, P=0.000), and was significantly higher in diabetic group than that in normal group (t=10.523, P=0.000) and CPDT intervention group (t=7.766, P=0.000). The mRNA level of retinal Nrf2 and HO-1 was significant different between all groups (FNrf2=19.503, PNrf2=0.000;FHO-1=9.737, PHO-1=0.001), and was higher in CPDT intervention group than the diabetic group (tNrf2=3.399, PNrf2=0.002;tHO-1=2.167, PHO-1=0.039). The protein level of retinal Nrf2 and HO-1 was significant different between all groups (FNrf2=112.823, FHO-1=119.361; P=0.000), and was higher in CPDT intervention group than the diabetic group (tNrf2=6.203, tHO-1=6.388; P=0.000). Immuno-staining showed that Nrf2 and HO-1 were mainly expressed in retinal ganglion cell layer, inner plexiform layer and inner nuclear layer, and were significant different between all groups (FNrf2=16.206, FHO-1=46.790; P=0.000). They also were higher in CPDT intervention group than the diabetic group (tNrf2=3.172, PNrf2=0.003;tHO-1=6.321, PHO-1=0.000), was higher in diabetic group than that in normal group (tNrf2=2.679, PNrf2=0.011;tHO-1=3.482, PHO-1=0.001). ConclusionCPDT may activate Nrf2/ARE pathway, induce Nrf2 and HO-1 expression, decrease serum MDA and blood glucose, and thus reduce oxidative stress injury in the retina of type 2 diabetic rats.