Diabetic retinopathy (DR) is a serious complication of long-standing diabetes mellitus. It affects about 25% of all patients with diabetes mellitus and causes a significant decrease in the quality of life. Despite many years of research, the exact pathway that leads to the development and progression of DR is not clear. Recent studies suggest that polyunsaturated fatty acids (PUFAs) and their metabolites could play a significant role in DR. There is evidence to suggest that an imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DR. This implies that PUFAs and their metabolites that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DR.