Abstract: OBJECTIVE To understand the distribution characteristics and drug resistance changes of Pseudomonas aeruginosa nosocomial infection, so as to provide guidance for the rational use of antibiotics, and provide a better basis for prevention and control of key areas. METHODS P. aeruginosa isolated from the laboratory department of Wenzhou central hospital from Jan. 2016 to Dec. 2019 were selected. The drug resistance and department distribution were analyzed using Whonet5.6 software. RESULTS From 2016 to 2019, 13 116 strains of Gram-negative bacilli and 1 662 strains（12.67%） of P. aeruginosa were isolated, ranking third for 4 consecutive years, mainly distributed in the following departments, 282 strains（16.97%） in intensive care unit, 200 strains（12.03%） in the department of respiratory medicine, 171 strains（10.29%） in the cadre ward, 135 strains（8.12%） in the tuberculosis ward, and 125 strains（7.52%） in the department of radiotherapy and chemotherapy, which showed an increasing trend annually in intensive care unit, chemoradiotherapy, rehabilitation and neurosurgery（P＜0.05）. The main sources of the specimens were 1336 strains（80.39%） in sputum, 99 strains（5.96%） in urine, 80 strains（4.81%） in pus and secretion. There was no significant difference in the distribution between different years. The drugs with lower resistance rates of P. aeruginosa were amikacin（1.39%）, tobramycin（3.97%） and four-generation cephalosporins（8.30%）; The drugs with higher resistance rates were ticacilin/caravic acid（32.10%）, imipenem（31.97%）, meropenem（21.83%）, etc; The annual change of drug resistance rate of carbapenems, aminoglycosides and enzyme inhibitors in P. aeruginosa showed no significant difference; Drug resistance of three-generation cephalosporins, four-generation cephalosporins and quinolones ciprofloxacin showed a decreasing trend year by year（P＜0.05）, while levofloxacin showed an increasing trend year by year（P＜0.05）. CONCLUSION P. aeruginosa was characterized by high clinical detection rate, wide distribution in departments, and serious drug resistance. The monitoring and intervention measures of antibiotic use should be strengthened in the hospital, especially in the key department to strengthen the management mechanism.