The receptor for glycation end-products RAGE was previously shown to play a central role in the development of diabetic neuropathy. The present study was aimed to investigate, whether plasma levels of the soluble forms of RAGE are associated with neuropathy in type 2 diabetes. One-hundred and eight patients were screened for peripheral and autonomic diabetic neuropathy using standardized screening tests. No differences in the levels of soluble RAGE or the more defined endogenous secretory RAGE were observed in patients categorized into having no, mild, moderate, or severe deficits in the neuropathy disability or symptom score. In bivariate analysis, neither soluble RAGE nor endogenous secretory RAGE correlated with the expiration to inspiration ratio of heart rate variability. In multivariate models, the neuropathy disability score was independently associated with age (beta=0.38, p<0.01), glomerular filtration rate (beta=0.28, p<0.01) and the presence of retinopathy (beta=0.27, p<0.01), while the neuropathy symptom score was associated with age (beta=0.31, p<0.01) and fasting glucose (beta=0.24, p<0.05). The expiration to inspiration ratio of heart rate variability was associated with age (beta=-0.42, p<0.01), the body-mass-index (beta=-0.28, p<0.01) and presence of retinopathy (beta=-0.19, p<0.05). In contrast to classical risk factors, plasma soluble RAGE and endogenous secretory RAGE are not associated with measures of diabetic neuropathy in type 2 diabetes patients.