Background: LCB01-0371 is a novel oxazolidinone compound containing a cyclic amidrazone group that shows potent anti-mycobacterial activities against most mycobacterial bacilli, including the multi-drug resistant tuberculosis. LCB01-0371 was evaluated for safety, tolerability, and pharmacokinetics in a recently completed phase I clinical trial. In this study, intracellular activity of LCB01-0371, against Mycobacterium tuberculosis was evaluated in comparison with that of Linezolid using macrophage infection models. Methods: Resazurin reduction microplate assay (REMA), was performed to determine the MIC of Mycobaterium tuberculosis against LCB01-0371 and linezolid. Human THP-1 macrophages were infected with H37Rv-GFP (MOI ratio 10). LCB01-0371 and linezolid treated each concentration for 5 days. Live cell microscopy using a automated live cell imager (BioTek Instruments). Fluorescent images of live cells were captured every 6 hrs for 5 days. Results: LCB01-0371 and linezolid exhibited minimum inhibitory concentration (MIC) values against Mycobacterium tuberculosis (H37Rv) 3.34uM and 0.55uM respectively. In a macrophage infection model, LCB01-0371 dramatically decreased the number of intracellular Mycobacterium tuberculosis bacilli at 5 days after infection at concentration range from 50 nM to 3.2 uM. LCB01 0371 and linezolid inhibited mycobacterial growth 28.54% and 21.76% respectively at concentration of 3.2 uM. Conclusions: Critically, we describe a class of oxazolidinone compounds, LCB01-0371, which reduces mycobacterial survival in macrophage infections, hence confirming the potential of LCB01- 0371 as a therapeutic drug target and suggesting that LCB01-0371 would be a novel candidate for the treatment of infectious diseases caused by mycobacterium tuberculosis.