The new cases of tuberculosis mainly come from the relapse of latent tuberculosis infection (LTBI), and the growing proportion of drug­-resistant Mycobacterium tuberculosis (DR­Mtb) among LTBI makes DR­LTBI the key point of tuberculosis prevention and control. The animal model of DR­Mtb latent­relapse infection is the foundation for basic research, anti-­DR-­Mtb drug development and vaccine evaluation. However, the lack of a DR­-Mtb animal model today presents a hurdle. The animal model of latent­-relapse infection based on drug­-sensitive strain H37Rv still has concerns such as high bacterial loads in the latent phase and large variation in the relapse phase in mice, and unpredicted latent and relapse phases in monkeys. These concerns limit its application. Furthermore, the lack of immune parameters in the evaluation makes the forward relapse unpredicted. The strategies and research progresses on the improvement of the current models are reviewed in this paper.