Diabetes afflicts an estimated 171 million people worldwide. Diabetic patients are at risk of a wide range of complications including peripheral neuropathy (or diabetic foot). The condition if left untreated will lead to ulcers and eventually lower extremity amputation. Current existing diagnostic techniques for peripheral neuropathy are mostly qualitative procedures based on patient sensations and exhibit significant inter- And intra-observer differences, and an economical quantitative diagnostic technique is still lacking. A system for quantitative early detection of diabetic peripheral neuropathy has been developed based the thermal response of the feet of diabetic patients following cold stimulus. This paper describes the details of the new system, which includes the following key components: (1) A new protocol of using thermal imaging as functional imaging to measure thermal response. (2) Segmentation and tracking of regions of interest (ROIs) for thermal videos. (3) A novel bio-heat transfer model based on thermoregulation. We also report our preliminary patient studies based on two classifiers, which gave strong evidence that the system can used for early quantitative detection of peripheral neuropathy for diabetics. Copyright © 2007 by the Association for Computing Machinery.