Starting with the vertical supply chain management of retail enterprises, the urban logistics distribution network among suppliers, retailers and multi-distribution centers are taken into account, which is studied for the vehicle routing problem of multi-distribution centers with cross-docking. Based on the operating guidelines and implementing requirements of cross-docking, the cross-docking is divided into stages, namely, the pickup and delivery operation. The time simultaneous arrival and cooperation of the vehicle are set up, and the delivery process which can be split is designed to meet the supply needs of many types of products. The model of vehicle routing problem of multi-distribution centers with cross-docking is built with a minimum of operational cost and transportation cost. According to the characteristics of the model, an improved genetic algorithm is proposed. Finally, the feasibility and effectiveness are verified by simulation. The results show that the cross-docking can effectively serve the timely supply of urban retail stores, and have some significant advantages in terms of the delivery time and transportation cost.