In this paper, a mathematical model is developed for economic design of multi-stage distribution system that consists of factory, central distribution centers, local distribution centers and retailers. The retailers are supplied products from different stage suppliers according to order size. The retailers are supplied products from factory if demand amount is large, central distribution center if medium, local distribution center if small. The economic design is to determine the economic size of facility factors that consist of distribution system. The cost factors are transportation cost from supply places to demand places, handling cost at distribution centers and inventory holding cost at retailers. It is to determine the transportation route of each retailer, the size and number of the vehicle at factory and distribution centers, the handling amount at distribution centers in order to minimize the total costs. The mathematical model is represented, the solution procedure is developed, and a numerical example is shown.