In this study we measured the levels of neuron-specific enolase mRNA as a possible marker of diabetic neuropathy. Blood samples were collected from healthy controls (n= 26), diabetic controls (no known neuropathy or retinopathy) (n= 22), and diabetics with clinically diagnosed neuropathy (n= 24) into PAXgene blood RNA tubes. mRNA was extracted, reverse-transcribed to cDNA, and measured by real-time quantitative PCR. Enolase mRNA levels were normalized by the simultaneous measurement of beta-actin mRNA. The results showed that the enolase mRNA was significantly (P= 0.002) higher in the diabetic control (median = 0.018; range = 0.006-0.037) group compared to healthy subjects (median = 0.0086; range = 0.0016-0.039). However, the diabetic neuropathy group showed lower enolase levels (median = 0.0067; range = 0.0025-0.017) compared to both healthy subjects (P= 0.06) and diabetic controls (P < 0.001). In the diabetic neuropathy group patients with preproliferative (median = 0.01; range = 0.008-0.017) or proliferative retinopathy (median = 0.011; range = 0.007-0.015) had significantly (P= 0.001) higher enolase mRNA compared to patients with background retinopathy (media = 0.004; range = 0.0025-0.0092). It is concluded that levels of enolase mRNA are decreased in diabetic neuropathy and this molecular marker may also be useful in differentiating early from advanced eye disease in those diabetics diagnosed with neuropathy.