With the increasing complexity of the distribution environment, customers usually propose higher requirements, such as independent loading of local and foreign cold-chain items in the event of an emergency. Moreover, minimum fuel volume plays an important role in the process of transportation with different speeds and different kinds of vehicles. In this paper, we present a new mathematical model to characterize cold-chain vehicle routing optimization with independent loading of local and foreign items and minimum fuel volume. To address the above mathematical model, an extended particle swarm optimization (PSO) algorithm is proposed by combining original PSO with 2-opt optimization to improve diversity and reduce convergence speed. Six sets of experiments are set to verify the practical performance and stability of the extended PSO algorithm based on three standard datasets of C201, R201, and RC201 from Solomon.