A two Echelon Location-Routing Problem （2E-LRP） solving model considering facility sizing decision was proposed to address the issues of unreasonable infrastructure layout and space utilization in the existing e-commerce industry. Firstly， differential facility sizing constraints were introduced into the traditional 2E-LRP， different combinations of facility sizes were designed by identifying customer base， the total cost composition was adjusted by using changes in size， and a 2E-LRP model considering facility size change with the minimum operating cost as goal was established. Secondly， a two-stage hybrid iterated local search heuristic algorithm was proposed for solving the model. Finally， the performance of the proposed model and optimization algorithm were analyzed and verified with examples in different datasets such as Prodhon. Experimental results show that the proposed model is universal for regional differences and different data sizes， and there is an inverse relationship between the total cost and the change range of facility size. Compared with the optimal costs of algorithms such as Lagrangean Relaxation Granular Tabu Search （LRGTS）， the average value of the optimal cost of the proposed algorithm on all instances is reduced by 6.67%， which can effectively save the operating cost.