The objective of the present study was to compare the activities of six combination regimens that currently being applied in clinical trials,including Isoniazid (H),Ethambutol (E),Pyrazinamide (Z),and the traditional second-line drugs Amikacin (A),Protionamide (Pt),Levofloxacin (L),Moxifloxacin (M),and Clofazimine (C),in a murine tuberculosis model using an MDR isolate.All drugs were administered for 2 months,while A was given five times weekly for the first month and twice weekly for the second month.After 1 month of treatment,all the combination regiments dramatically reduced CFU counts in the spleens and lungs,especially the regimens that containing 6 drugs had no visible counts in the both organs.After 2 months of treatment,the spleens of mice treated with the 6 regimens all became culture negative,but for the lungs,just that treated with the regimens containing 6drugs became culture negative.When L was replaced by M,the regimen displayed a better activity.The activity of A is closely related to the dosage.Despite in vitro resistance,H showed moderate activity.C could improve the combination therapy results,although its place in the treatment of tuberculosis is not clear.After 3 months post treatment,both the spleens and lungs of mice treated with the 2 regimens containing 6 drugs remained culture negative,while the spleens of mice treated with the other 4 regimens became culture positive.The more drugs were included,the better activity was showed.