Objective: Oxidative stress plays an important role in the pathogenesis of diabetic retinopathy. The aim of the present study was to investigate the effect of Crocus sativus L. styles (saffron) extract on oxidative stress indices of retina in streptozotocin (STZ)-induced diabetic rats. Methods: Adult male Wistar rats (n=20) were randomized into the following 4 groups (n=6-7/ group): Control group (C): normal, Control + Saffron group (CS): non-diabetic rats treated with 60 mg/ kg of saffron extract, Diabetic group (D) and Diabetic + Saffron group (DS): diabetic rats treated with 60 mg/ kg saffron extract. We determined the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) as markers of antioxidant response, as well as malondialdehyde (MDA) as a marker of lipid peroxidation. Results: Induction of diabetes caused a significant decline in the activities of CAT (76.43%), SOD (53.43%) and GPx (77.58%). MDA levels were significantly lower in the DS group (0.878 ± 0.375 nmol MDA/ mg protein) as compared to D group (1.950 ± 0.299 nmol MDA/ mg protein, p<0.01) and in the CS group (0.503 ± 0.221) in comparison to C group (1.699 ± 0.454, p<0.01). Moreover, SOD and GPx activities were significantly higher (more than 1.5 and 3.5-fold respectively) after treatment with saffron (p<0.01). Regarding the retinas of non-diabetic animals, the administration of the extract caused an > 1.8-fold increase in the activity of CAT (p<0.05) and a 3-fold decrease in MDA levels (p<0.01). Conclusions: This study showed that saffron extract has a protective antioxidant action in retinas of diabetic rats. Abbreviations: C = Control group, CS = non-diabetic rats diabetic rats treated with 60 mg/ kg saffron extract, D = diabetic group, DS = diabetic rats treated with 60 mg/ kg saffron extract, SOD = superoxide dismutase, GPx = glutathione peroxidase, CAT = catalase, MDA = malondialdehyde, DM = diabetes mellitus, DR = diabetic retinopathy, ROS = reactive oxygen species, STZ = streptozotocin, GSH = reduced glutathione