In the non-invasive blood glucose measurement (NBGM) based on near-infrared spectroscopy, the established blood glucose prediction model could not work well for a long time as it is greatly affected by the fluctuation of human skin status. It can be a limitation for the real clinical application of the method. Cut aneous blood perfusion (CBP) is a parameter closely related to the physiological state of the skin, which directly affects the water flow in the skin. It is also difficult to be controlled by external means like the approaches to control the temperature or contacting pressure. As for measuring skin spectra, CBP affects the thickness of the dermis indirectly by changing the migration of water, and the skin spectra change greatly. In this paper, Monte Carlo simulation is used to simulate the diffuse light intensity, photon penetration depth and average optical path of a three-layered skin model when the thickness of the dermis changes ±30 microns at 1 000~1 700 nm. The spectral changes were investigated. The differential processing can be used on the diffuse attenuations of two neighbored source-detector separations (SDSs) to eliminate the influence of dermis thickness change. The appropriate SDSs are acquired to perform the differential measurement for 1 000~1 700 nm wavelengths. It has been found that 1 200 nm should be an optimal wavelength to get away from the affection from the varying dermis thickness because the attenuation at all SDSs varies little. At the wavelengths near 1 450 nm, where the water has strong absorption, the attenuation will change rapidly with SDS in certain SDSs, requiring a critical SDS selection. For the commonly used wavelengths in NBGM, 1 200, 1 300 and 1 600 nm, the SDSs can be set in which is less than 0.1 cm or greater than 0.4 cm since there the attenuation changes slowly with the SDS and the differential on two SDSs can work well to reduce the influence of the change of dermis thickness. Moreover, the SDSs should be selected to primarily sense the information of the dermis considering the different percentages of photons in the dermis, where 80% photon percentage is taken as the threshold to choose the SDSs. Finally, for 1 200, 1 300 and 1 600 nm, two appropriate SDSs can be picked in 0.03~0.1 cm to suppress the influence of dermis thickness change and achieve the desired measurement accuracy by the current instruments. This study could be a solution to reduce the influence of CBP.收稿日期>2022-02-22