Objective: To investigate the clinical characteristics, distribution of pathogenic bacteria and changes of drug sensitivity resistance of diabetes with bloodstream infection in order to provide theoretical basis for clinical diagnosis and treatment of patients with diabetes and bloodstream infection. Methods: The clinical data, pathogen distribution, drug sensitivity results, and disease outcomes of 549 patients with diabetes and bloodstream infection who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2013 to December 2018 were collected. At the same time, 2 196 patients with non-diabetic bloodstream infection who were hospitalized from January 2013 to December 2018 were used as a control group to compare clinical data, bacterial distribution, and drug resistance rates between the two groups. At the same time, the change trend of antibiotic resistance rate of main pathogenic bacteria in the two groups was analyzed. Results: A total of 597 strains were detected in 549 cases in the DM group and a total of 2 479 strains were detected in 2 196 cases in the non-DM group. The proportion of Gram-positive bacteria was lower in the DM group than that in the non-DM group, and the proportion of Gram-negative strains was higher than that in the non-DM group, and the difference was not statistically significant (P>0.05); the proportion of Staphylococcus aureus detected in the DM group was slightly higher than that in the non-DM group, and the difference was statistically significant (P=0.017); the resistance rate of Escherichia coli in the two groups to ampicillin, cefazolin, levofloxacin and ciprofloxacin was over 50%; the resistance rate of Escherichia coli to carbapenem antibiotics in the non-DM group was significantly higher than that in the DM group (P<0.05), and there is an increasing trend year by year (P<0.05). Conclusion: Gram-positive bacteria are the main pathogens in patients with diabetes and bloodstream infections. The common Gram-positive bacteria are Staphylococcus epidermidis, Staphylococcus aureus, and Staphylococcus hominis. There is a certain difference in antibiotic resistance between the bloodstream infection pathogens of diabetic and non-diabetic patients, and there is also a difference in the trend of drug resistance. Paying close attention to the trend of drug resistance of common pathogens in bloodstream infection may provide guidance for the rational use of antibiotics in clinical practice.