Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM), and its pathogenesis remains incompletely understood. Research has identified inflammation as a key factor in the onset and progression of DR. As a group of systemic metabolic disorders, the dysregulation of polyunsaturated fatty acid (PUFA) metabolism induced by DM is closely related to the inflammatory mechanisms in DR. Recent metabolomic studies have revealed that in various stages of DR and in diabetic animal models, most upregulated PUFAs and their derivatives act as pro-inflammatory mediators, while downregulated PUFAs and their derivatives are predominantly anti-inflammatory. In the progression of DR, some PUFAs may exert anti-inflammatory effects by inhibiting microglial activation, reducing the expression of inflammatory proteins, antagonizing the pro-inflammatory effects of arachidonic acid, and suppressing the activation of inflammasomes and the migration of neutrophils. Conversely, other PUFAs may promote inflammation through mechanisms such as the formation of pro-inflammatory mediators resembling prostaglandins, facilitating leukocyte adhesion, and inducing oxidative stress responses. PUFAs play a complex dual role in the inflammatory mechanisms of DR. A deeper understanding of these mechanisms not only aids in elucidating the pathogenesis of DR but also provides potential targets for developing new therapeutic strategies.