Abstract: Purpose A high fructose diet has been widely used to trigger insulin resistance in rodent; insulin resistance is one of the major risk factor for the development of type 2 diabetes. Thirty to 40% of diabetic patients develop diabetic retinopathy. In this study, we aimed to evaluate the short-term effect, at 1, 3, 5, 8 days, of a 60% fructose diet, on photoreceptor sensitivity and gene expression in the retina of Brown Norway rats. Methods: Flicker electroretinograms (8Hz) were recorded under anesthesia, from both eyes simultaneously in order to study sensitivity of photoreceptors. Then, rats were euthanized and enucleated. Retinae and posterior poles were collected to analyze gene expression by RT-PCR. We specifically focused on 45 genes involved in cholesterol homeostasis, lipid trafficking, vascular changes and inflammation. Results: Our data showed that a short period of fructose feeding induced early changes in retinal functionality and homeostasis. Interestingly, we reported a partial loss of cone sensitivity after 8 days of feeding rats with the high-fructose diet. No effect was found in rod sensitivity. Conclusion: These findings are consistent with the sensibility and susceptibility of cones to dietary changes. These data deserve further investigations on the cross-talk between cones and rods upon metabolic changes associated with aging.