Despite well-known limitations, mice remain useful as model animals to study tuberculosis (TB) pathogenesis, the basic immune response, the extent of lung pathology as well as efficacy of new drugs against Mycobacterium tuberculosis[1,2]. There are four routes of tuberculosis infection in mice: aerosol generation and exposition, intravenous injection, intranasal administration, and subcutaneous administration[3], and the first two are the most commonly used. The low-dose aerosol model was found to best fit the dissemination of TB cases in the community while intravenous infection is useful to study strain virulence[4]. Intra-nasal and intra-tracheal inoculation techniques have a high degree of variability in the delivery of bacilli into the alveoli and the generation of an aerosol cloud of very small droplet nuclei containing the bacilli was shown to be the most reproducible method[1]. In the case of the intravenous tail injection, the administered doses are higher compared to the aerosol route. The intravenous infection leads to the initial infection established in the lungs followed by the dissemination of the bacteria through the body of the animal. The genetic background of mice plays an important role in susceptibility to the infection and further progression to disease. Intravenous infection can lead to a rapid development of disease and an increased animal lethality after 28 days of the infection but this concerns susceptible C3H/HeJ mice lineage and not resistant C57BL/6 lineage[5]. The latter is resistant to infection and develops severe pulmonary damage after a long period since intravenous infection, around 200 days. Therefore, this design is relevant to study the virulence and is appropriate for observation of the long-term therapy of multi-drug resistant (MDR) M. tuberculosis infection.