To determine levels of apolipoprotein (apo) A-I and apo H in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and to examine whether apo A-I and apo H messenger RNA (mRNA) levels are overexpressed in the diabetic retina.Vitreous samples from 4 diabetic patients with PDR and 8 nondiabetic patients with macular hole were selected for proteomic analysis. Fourteen additional samples (7 from patients with PDR and 7 from patients with macular hole) were used for Western blot analysis. Fourteen postmortem eyes (7 from diabetic and 7 from nondiabetic donors) were used to perform quantitative real-time polymerase chain reaction analysis.Intravitreous apo A-I and apo H levels were significantly higher in patients with PDR than in the control group. The apo A-I and apo H mRNA levels obtained from the retinas of diabetic donors were significantly higher than those obtained from nondiabetic donors. Retinal pigment epithelium was the main contributor to the differences.Levels of apo A-I and apo H are elevated in the vitreous fluid of diabetic patients with PDR. In addition, we provide the first evidence, to our knowledge, that a higher expression of apo A-I and apo H mRNAs exists in the diabetic retina.The results of this study may be relevant to new treatment strategies aimed toward reducing the development of diabetic retinopathy.