Objective To investigate the distribution and antimicrobial resistance change of respiratory bacteria isolates from Hunan Province Antimicrobial Resistance Surveillance System in 2012-2021. Methods Bacterial identification and antimicrobial susceptibility testing were performed according to technical scheme of China Antimicrobial Resistance Surveillance System (CARSS), duplicate strains were eliminated. Antimicrobial susceptibility was judged according to the standards from American Clinical and Laboratory Standards Institute (CLSI) 2022, statistical analysis was conducted with WHONET 5.6 software. Results A total of 976 984 bacteria strains isolated from respiratory specimens were collected in Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021. 185 642 strains (19.0%) were Gram-positive and 791 342 (81.0%) were Gram-negative bacteria. The top 5 bacteria isolated from respiratory specimens of adult patients were Klebsiella pneumoniae (25.2%), Pseudomonas aeruginosa (17.0%), Acinetobacter baumannii (14.6%), Escherichia coli (6.7%) and Staphylococcus aureus (5.8%). The top 5 bacteria isolated from respiratory specimens of pediatric patients were Staphylococcus aureus (17.7%), Streptococcus pneumoniae (15.6%), Escherichia coli (13.5%), Klebsiella pneumoniae (13.1%) and Haemophilus influenzae (10.8%). Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae showed lower resistance rates to tigecycline, cefoperazone/sulbactam, piperacillin/tazobactam, carbapenem and amikacin (< 15%). The resistance rates of Klebsiella pneumoniae to imipenem and meropenem increased from 3.5% and 4.2% in 2012-2013 to 9.5% and 11.5% in 2020-2021, respectively, resistance rates to cefoperazone/sulbactam, piperacillin/tazobactam, amikacin, tobramycin, ciprofloxacin and levofloxacin showed an upward trend. Resistance rates of Escherichia coli and Enterobacter cloacae to aztreonam, aminoglycosides, and fluoroquinolones showed a downward trend. Resistance rate of Pseudomonas aeruginosa to polymyxin and resistance rates of Acinetobacter baumannii to tigecycline and polymyxin were all lower (all < 6%). Resistance rates of Pseudomonas aeruginosa to β-lactams, aminoglycosides and fluoroquinolones decreased. Resistance rate of Acinetobacter baumannii to cefoperazone/sulbactam increased from 18.0% to 43.7%, to piperacillin/tazobactam, imipenem, fluoroquinolones and minocycline showed an upward trend. No Staphylococcus aureus strain was found to be resistant to vancomycin, teicolanin and linezolid. Isolation rates of methicillin-resistant Staphylococcus aureus(MRSA) from adult and pediatric patients were 37.8% (14 208/37 594) and 22.7% (10 874/47 882), respectively. Conclusion Gram-negative bacteria was the main bacteria isolated from respiratory specimens in Hunan Province Antimicrobial Resistance Surveillance System in 2012-2021. The predominant bacterial species isolated from adults and pediatric patients were different. The resistance rates of Escherichia coli, Enterobacter cloacae and Pseudomonas aeruginosa to partial antimicrobial agents decreased year by year. The resistance rate of Klebsiella pneumoniae to carbapenems increased gradually. Continuous and efficient surveillance on antimicrobial resistance should be carried out to provide data basis for clinical antimicrobial use.