Abstract: In the present research, we decided to study the drug resistance rate of isolated strains to the first line of anti mycobacterium drugs: isoniazid, rifampine, ethambutol and streptomycin. All tuberculosis patient who referred to Bou-Ali hospital (the only center for training and treatment of Infectious disease in Sistan and Baluchestan province) during March 2001-July 2003 whose sputum sample smear byZNCF staining were found positive, were included in our study. After primary culture and subsequent passages, the strains of Mycobacterium tuberculosis were identified and isolated according to the growth rate, pigmentation and biochemical tests. Subsequently, drug sensitivity test of isolated was carried out by proportional standard method. In this study on 84 isolated strains of Mycobacterium tuberculosis from patients who referred to Zahedan Bou Ali hospital during March 2001-July 2003 demonstrated drug resistance to Rrifampin, Isoniazid, Streptomycin and Ethambutol was 55.9, 39.2, 33.3 and 27.3%, respectively. Present findings indicated that the prevalence of drug resistance against first line of anti TB drugs will gradually became a serious problem and targeted programs for reduction of these resistance rates is essential.