Based on the unblocked reliability theory of the road network, combined with the characteristics of the logistics distribution of expressway service areas, the concept of network unblocked reliability on logistics distribution was put forward. Under the reliability analysis, the optimization model of multi objective, multi depot and open vehicle scheduling on logistics distribution of highway service areas was established, and the ant colony algorithm was designed. In the end an example was analyzed to validate the usability of the optimization model by comparing with saving mileage, which demonstrates the established optimization model of multiple depot vehicle scheduling is of a better practical value to guide the optimization decision making of logistics distribution network and to improve the reliability of logistics distribution of expressway service areas.