The guest exchange mechanism in the clathrate phase of syndiotactic polystyrene (sPS) was investigated by ATR-FTIR spectroscopy utilizing the selectivity of the sPS crystalline region about the conformation of 1,2-dichloroethane (DCE). 1,2-Dichloroethane (h-DCE) and its deuterated compound (d-DCE) were used as guests to analyze the sorption behavior of the sorbate molecules and the desorption behavior of the guest molecules stored in the crystalline region beforehand, simultaneously. The spectral changes on the exposure of an sPS film containing d-DCE to h-DCE vapor were followed, and the information about the guest exchange processes in both the crystalline and amorphous regions were obtained. In the earliest stage, the exchange occurred mainly in the amorphous region, while the exchange in the crystalline region proceeded gradually for a long time. On the basis of this finding, the diffusion coefficients of DCE molecules in the crystalline and amorphous regions were estimated.