The rates of protein conformational changes are not only limited by external but also internal friction, however, the origin and significance of this latter phenomenon is poorly understood.Recently, by varying the viscosity and the temperature of the external medium, we determined experimentally both the magnitude and the temperature dependence of the internal friction of trypsin during its conformational change.We found that the temperature dependence followed an Arrhenius-like behavior with an activation energy in the range of tens of kJ/mol.This indicates that the internal structural rearrangement of proteins occurs in a rugged energy landscape.