In noninvasive blood glucose measurement, it is difficult to keep the contact area between skin and internal reflectance element uniform while the mid-infrared spectra of human skin are taken, and this would lead to path-length variations. To study the effect of path-length variations on PLSR calibration model, in the present paper, according to the correlation coefficients between path-lengths and glucose concentrations, two PLSR models were achieved respectively and RMSECV were 31.3 and 4.52 mg·dL-1, RMSEP were 30.3 and 98.7 mg·dL-1 for the validation set. The results show that the chance correlations between path-lengths and glucose concentrations will lead to calibration models with different accuracy and robustness. This is useful to improving the reliability of noninvasive measurement of blood glucose by mid-infrared spectroscopy.