This work aimed to study the effect of the coolant amount on the temperature control of extruded polystyrene insulation box. Different amount of coolant was added into the box at three different external temperature and humidity conditions. Influences of the coolant amount on temperature control effect of extruded polystyrene insulation box were studied. When different amount of coolant was added, the temperature holding time at different sites in the insulation box was different, but a common law was obeyed. The temperature distributing law inside the extruded polystyrene insulation box was that the holding time of the bottom test point was longer than the middle than the top. When the mass ratio of coolant and refrigerated drugs was 4∶1, the holding time of the box could reach 24 hours at 23 ℃ and 50% RH. And the 3D model of central point about the external temperature and mass ratio of coolant and refrigerated drugs and holding time was built. The temperature inside the insulation box could be controlled at 2-8 ℃ by combining the extruded polystyrene box and coolant, which could meet the requirement of temperature control for short-distance transportation of refrigerated drugs.