The relationship between lipids and the development and/or severity of diabetic retinopathy (DR) is complex. Large epidemiologic studies suggest an inconsistent and overall modest association between serum triglycerides or major cholesterol species and the severity of DR; however, certain specific lipoprotein species may have stronger associations with DR severity, suggesting a pathophysiological role for lipoproteins analogous to that seen in atherosclerosis. In this lipoprotein-mediated DR pathogenesis model, damage to the blood-retinal barrier allows extravasation of lipoprotein species, which are modified in the intraretinal environment, creating substantial local damage. Additionally, hypolipidemic therapy with statins and fibrates--particularly the latter--have been shown to modulate DR in large-scale studies. Since serum lipid profile changes do not necessarily correlate with DR modulation, the efficacy of these agents may be due to their tissue-specific changes in lipoproteins and/or their anti-inflammatory, antioxidative, antiangiogenic, and antiapoptotic functions.