Objective To investigate the drug resistance of Mycobacterium tuberculosis in diabetes melli⁃ tus and pulmonary tuberculosis comorbidity（DM⁃TB）. Methods A retrospective case⁃control study was conducted to review and analyze the clinical data of 1948 patients who was diagnosed with DM⁃TB in the inpatient and outpa⁃ tient departments of Guangzhou Chest Hospital from January 2018 to December 2020. A total of 1012 cases with positive Mycobacterium tuberculosis culture and drug susceptibility results were screened out. After excluding the cases with incomplete data，438 cases with complete data were included for analyses of age，gender，haemoglo⁃ bin，albumin，glycatedhaemoglobin（HbA1c），extent of lesions，number of cavities，treatment history，sputum bacterial load and rifampicin resistance. The description method and Pearson Chi ⁃ square test（χ2 ）were used to compare analyze the first and second line drug resistance of the strains from the 1012 patients. Among the selected cases，？86 patients who were resistant against rifampicin were assigned as rifampicin⁃resistant（RR⁃TB）group， and then another 86 patients were randomly selected from the rest 352 patients sensitive to rifampicin by random digit table method as rifampicin ⁃sensitive（RS ⁃TB）group.The methods of？t ⁃test，rank ⁃sum test or Pearson Chi square test（χ2 ）were used for the analyses. The clinical characteristics of the included cases were taken as inde⁃ pendent variables and rifampicin resistance as dependent variables. Multivariate logistic regression analysis was per⁃ formed to screen out independent risk factors for RR ⁃TB in DM ⁃TB patients. Results Among the 1012 patients with TB⁃DM，the rate of rifampicin resistance was 13.3%，the rate of initial rifampicin resistance was 6.8%，the rate of retreatment rifampicin resistance was 45.9%，with significant differences（χ2 = 127.956，P = 0.000）. The rate of multidrug⁃resistance was 11.77%，the rate of initial multidrug⁃resistance was 5.5%，the rate of retreatment multidrug ⁃ resistance was 42.9%，with significant difference between the two groups（χ2 = 191.468，P = 0.000）. Multivariate logistic regression analysis showed that retreatment（OR = 9.517，95%CI：4.333 ~ 20.904，P = 0.000） was an independent risk factor for rifampicin resistance in the DM⁃TB patients，and senior ages（OR = 0.440，95%CI： 0.252 ~ 0.771，P = 0.004）was an independent protective factor. Conclusion The prevalence of rifampicin resis⁃ tance in DM⁃TB isrelatively high，especially among young patients and retreated patients. For DM⁃TB population， timely drug sensitivity test can help the early diagnosis and treatment of rifampicin⁃resistant tuberculosis.