Objective To understand the change in distribution and antimicrobial resistance of bacteria isolated from blood specimens of Hunan Province, and provide for the initial diagnosis and treatment of clinical bloodstream infection (BSI). Methods Data reported from member units of Hunan Province Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected. Bacterial antimicrobial resistance surveillance method was implemented according to the technical scheme of China Antimicrobial Resistance Surveillance System (CARSS). Bacteria from blood specimens and bacterial antimicrobial susceptibility testing results were analyzed by WHONET 5.6 software and SPSS 27.0 software. Results A total of 207 054 bacterial strains were isolated from blood specimens from member units in Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021, including 107 135 (51.7%) Gram-positive bacteria and 99 919 (48.3%) Gram-negative bacteria. There was no change in the top 6 pathogenic bacteria from 2012 to 2021, with Escherichia coli (n=51 537, 24.9%) ranking first, followed by Staphylococcus epidermidis (n=29 115, 14.1%), Staphylococcus aureus (n=17 402, 8.4%), Klebsiella pneumoniae (17 325, 8.4%), Pseudomonas aeruginosa (n=4 010, 1.9%) and Acinetobacter baumannii (n=3 598, 1.7%). The detection rate of methicillin-resistant Staphylococcus aureus (MRSA) decreased from 30.3% in 2015 to 20.7% in 2021, while the detection rate of methicillin-resistant coagulase-negative Staphylococcus (MRCNS) showed an upward trend year by year (57.9%-66.8%). No Staphylococcus was found to be resistant to vancomycin, linezolid, and teicoplanin. Among Gram-negative bacteria, constituent ratios of Escherichia coli and Klebsiella pneumoniae were 43.9%-53.9% and 14.2%-19.5%, respectively, both showing an upward trend (both P<0.001). Constituent ratios of Pseudomonas aeruginosa and Acinetobacter baumannii were 3.6%-5.1% and 3.0%-4.5%, respectively, both showing a downward trend year by year (both P<0.001). From 2012 to 2021, resistance rates of Escherichia coli to imipenem and ertapenem were 1.0%-2.0% and 0.6%-1.1%, respectively; presenting a downward trend (P＜0.001). The resistant rates of Klebsiella pneumoniae to meropenem and ertapenem were 7.4%-13.7% and 4.8%-6.4%, respectively, presenting a downward trend (both P<0.001). The resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem antibiotics were 7.1%-15.6% and 34.7%-45.7%, respectively. The trend of resistance to carbapenem antibiotics was relatively stable, but has decreased compared with 2012-2016. The resistance rates of Escherichia coli to the third-generation cephalosporins from 2012 to 2021 were 41.0%-65.4%, showing a downward trend year by year. Conclusion The constituent ratio of Gram-negative bacillus from blood specimens in Hunan Province has been increasing year by year, while the detection rate of carbapenem-resistant Gram-negative bacillus remained relatively stable in the past 5 years, and the detection rate of coagulase-negative Staphylococcus has shown a downward trend.