Objective To understand the distribution and changes in antimicrobial resistance of clinically isolated Pseudomonas aeruginosa (P. aeruginosa) in the member hospitals of Hunan Provincial Antimicrobial Resistance Surveillance System from 2012 to 2021. Methods Antimicrobial susceptibility testing by disk diffusion or automated instrument was performed on clinical isolates. Testing results were determined according to the standards of 2022 edition from American Clinical Laboratory Standards Institute (CLSI). Statistical analysis was performed by WHONET 5.6 software. Data were analyzed by trend test (Cochran-armitage) and Chi-square test with SPSS. Results A total of 176 441 strains of P. aeruginosa were surveilled by Hunan Provincial Antimicrobial Resistance Surveillance System from 2012 to 2021. 99.4% of the strains were isolated from hospitalized patients, and about 70% of the strains were isolated from respiratory specimens. 8.4% of P. aeruginosa were from children (0-17 years old), 91.6% were from adults. Antimicrobial susceptibility testing results showed that P. aeruginosa was most sensitive to polymyxin B over 10 years, with a resis-tance rate of less than 6%. Resistance rates to piperacillin, piperacillin/tazobactam, ceftazidime, cefepime, aztreonam, imipenem, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, and polymyxin B all showed downward trends. A total of 29 920 carbapenem-resistant P. aeruginosa (CRPA) strains were detected. The average isolation rate of CRPA in this province was 18.0% over 10 years. CRPA detection rate from adult was 18.5%, higher than that from children (12.3%), and both showing downward trends. Conclusion The resistance rate of clinically isolated P. aeruginosa in Hunan Province to most commonly used antimicrobial agents is decreasing.