The approaches of microcalorimetry and molecular dynamic simulation were adopted to investigate the protective effect caused by adding protectants.The results indicate that disaccharide protectants are able to maintain the molecular structure of insulin and contribute to the thermal stability of insulin due to the regional selective adsorption of protectants on the surface of insulin.Among four disaccharide protectants,the protectant with stronger adsorption ability conducts better performance in stabilizing the molecular structure of protein.With increasing the concentration of protectants,the thermal stability of insulin changes from increasing to gradually stable state.A further analysis upon the interaction between[JP]protectants and water reflects that increasing the thermal stability of insulin is attributed mainly to the interaction between insulin and disaccharides.