In the past two decades, the applications of optical monitoring for non-invasive assessment of glucose have been pursued with limited success. We have investigated potential application of optical coherence tomography (OCT) for non- invasive and continuous monitoring of blood glucose concentration. An OCT system with the wavelength of 1300 nm was used in phantom and in vivo studies. Polystyrene spheres with the diameter of 0.76 micrometers were used as scatterers in aqueous solutions in the phantom studies. We have found 4.5% change of the OCT signal slope as a function of glucose concentration in the range from 0 to 100 mM in the phantoms. This is in good agreement with theoretical calculations performed using Mie's theory. Bolus glucose injection and glucose clamping experiments were performed in New Zealand rabbits and Yucatan micropigs. OCT images were obtained from skin (dorsal area of the pigs and rabbit ear). Our pilot studies show close correlation between actual blood glucose concentration and slope of the OCT signals. The slope decreased substantially (about 40% in tissues in vivo) with the increase of blood glucose concentration from 4 to 30 mM. In conclusion, we have demonstrated that glucose-induced changes in optical properties of skin can be monitored by OCT suggesting that a new OCT-based optical sensor could be developed for sensitive and accurate non-invasive monitoring of glucose concentration in vivo.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.