One year ago, the coronavirus (COVID-19) virus began spreading around the world. Vaccines have now been developed by a variety companies from different countries. Vaccines must be stored in good condition within cold boxes designed to keep vaccines within acceptable temperature ranges. This paper proposes a hybrid algorithm based on a chemical reaction called Hybrid Artificial Chemical Reaction Optimization Algorithm (HACROA) which has been used to design a vaccine cold chain network in northern Thailand. The scope of this research is to focus on the Office of Disease Prevention and Control Area 1 (Chiang Mai, Thailand). The objective of this research is to rearrange routes to minimize total travel distances. Experiments were conducted to compare the efficiency of the hybrid algorithm with other algorithms in term of the distance. The optimal parameters of the algorithm employed a statistical experiment theory namely full factorial design. Experiment design and analysis were adopted to investigate the factors that affect the performance of this algorithm. HACROA was able to rearrange routes and found a better solution than the other algorithms.