Abstract: To investigate the lag of glucose concentration between interstitial fluid of human skin and blood (peripheral blood and venous blood) during rapid change of blood glucose, optical coherence tomography (OCT) was used to measure attenuation coefficient of human skin with the change of blood glucose in oral glucose tolerance test and glucose clamp in vivo. To reduce error in prediction result, the correlation region used to calculate predicted glucose concentration should be selected below 700m~800m in dermis layer. The results show that lag time decreases with the increases of depth of human skin. It is demonstrated experimentally that the lag time changes at different depths in human skin. The study can improve the accuracy and reliability of measurement value in noninvasive blood glucose sensing.