Abstract: Objective To investigate the microbiostatic mechanism of ethambutol(EMB),isoniazid(I N H)and rifampin(RIF),and to find differential expression proteins in Mycobacterium smegmatis mc² 155 cells treated by ethambutol,isoniazid and rifampin,respectively.Methods The total protein of untreated and ethambutol-,isoniazid-and rifampintreated mc² 155 cells were separated by ampholyte p H gradients based on two-dimensional gel electrophoresis(2-DE).The differentially expressed proteins were analyzed by using image analysis software.Results Control group and ethambutol-,isoniazid-and riampin-treated group contained 155,147,235 and 161 protein spots,respectively.Distributions of proteins of control group and ethambutol-,isoniazid-and rifampin-treated group have different pattern.Conclusion There is a significant difference in protein expression between untreated and ethambutol-,isoniazid-and rifampin-treated mc² 155 cells.It suggests that the differential expression analysis of proteomes may be useful to further elucidate microbiostatic mechanism of ethambutol,isoniazid and rifampin,and search for newdrug targets against TB.