Abstract: Objective: To evaluate the protective efficacy of MPT64 and ESAT6 DNA vaccines from M.tuberculosis. Methods: BALB/c mice were randomly divided into 5 groups and subjected to following treatments respectively, i.e. immunized with saline（A）,plasmid vector（B）,M.bovis BCG（C）,MPT64 DNA vaccine（D）or ESAT6（E）,and then infected by vein intraperitoneal injection with M.tuberculosis H37Rv. The liver and spleen histopathological changes were observed 5 or 10 weeks after infection by microscopy. Results: At 5 weeks after infection,the liver lesions in the mice of group A and B mainly showed moderate hyperemia and small tuberculous gronulomas consisted of numerous lymphocytes, macrophages, epithelioid cell,its quantity is 1～2/HPF. In the mice of group C,D and E, main pathological changes exhibited mild hyperemia and 3～7/HPF middling size tuberculous gronulomas.At 10 weeks after infection,mild hyperemia and middling size tuberculous gronulomas can be seen in group A and B,the number is 3～4/HPF, main pathological changes of group C exhibited mild hyperemia and middling size tuberculous gronulomas consisted of numerous lymphocytes and epithelioid cell, the number is 7～9/HPF, mild hyperemia and small tubercle can be found in group D,its number is 4～5/HPF,in groupE, outstanding pathological changes were mild hyperemia and middling size tubercle,the number is 4～8/HPF. At 10 weeks after infection,the spleen lesions in the mice of group A showed heavy hyperemia and hyperplasia of splenic lymph nodule,there is not abnormity in group B, the pathological changes in groupC is heavy hyperplasia and fusion of splenic lymph nodule,mild change can be seen in group D, moderate hyperplasia and fusion of splenic lymph nodule were found in group E.Conclusions: MPT64 and ESAT6 DNA vaccines from M.tuberculosis could enhance immunity against M. tuberculosis. The protective efficacy of ESAT6 DNA vaccine is stronger than that of MPT64 DNA vaccine, but not stronger than that of Mycobacterium bovis BCG.