The two-echelon distribution network in supply chain with multi-depository and multi-distribution places is studied. From the viewpoint of upper and lower enterprises in supply chain, a bi-level programming model is put forward to describe the problem about the operational designing of the two-echelon distribution network, which aims to minimize the cost of logistics for each enterprise. The solution of the model is discussed and an effective algorithm based on the idea of layered iteration is given. Finally, the emulational calculation with the model is carried out on computer.