Objectives: The aim of this study was to investigate how melatonin administration affects retinal oxidative damage and retinal SIRT1 gene activation in diabetic elderly female rat model. Methods: 16-months-old female rats were used in the study. A total of 24 rats were divided into 4 groups in equal numbers: Group 1. Control, Group 2. Control + Melatonin, Group 3. Diabetes, Group 4. Diabetes + Melatonin. In group 3 and 4 rats, diabetes was induced by intraperitoneal (IP) injection of streptozotocin. Groups 2 and 4 were given ip melatonin for 4 weeks. SIRT-1 gene expression was determined by PCR method and GSH and MDA levels by ELISA in retinal tissue samples taken from animals sacrificed under general anesthesia. Results: In our study, the highest retinal SIRT1 expression values were obtained in the diabetes + melatonin (G4) group. The retinal SIRT1 expression values of the diabetes group (G3) were lower than group 4 and higher than the general control (G1) and control + melatonin (G2) groups. Again in our study, the highest retinal MDA values were obtained in the diabetes group (G3). The highest retinal GSH values were obtained in the Diabetes + melatonin group (G4). Conclusion: The results of our study showed that melatonin supplementation has a protective effect on retinal tissue in a diabetic elderly female rat model. This protective effect of melatonin supplementation occurs by increasing both retinal antioxidant activity and retinal SIRT1 gene expression.