Abstract: The structural information of proteins was studied with hydrogen/deuterium exchange mass spectrometry by testing the hydrogen(deuterium) on protein bond exchange with the deuterium(hydrogen) in solvents. Utilizing hydrogen/deuterium exchange technique combined with Fourier transform ion cyclotron resonance mass spectrometry, the hydrogen/deuterium exchange in deuterium-cellular retinoic acid-binding protein I and its solvents was investigated. At different pH, the different exchange mechanism and different exchange speed are found for this protein. From the speed of the hydrogen/deuterium exchange, the number of unexchangeing hydrogen or deuterium at different exchange time remained in protein can be estimated, confirming the extent of the protein bond exposure to the solvents to obtain the structural information of protein.