Abstract: OBJECTIVE The restudy of mechanism of macrolide drugs on pseudomonas aeruginosa (PA) is of high guidance for clinically treating PA infection and doing basic research. METHODS Retrieval through CAJ bibliographic database, analysis and research from the view of the antibacterial action mechanism of macrolide drugs on PA. RESULTS The action mechanism of macrolide drugs on PA infection is not through classic ribosomes (to combine with 50S subunits in bacterial ribosomes so to restrain the synthesis of bacterial protein) but to restrain or kill PA through immune regulation, anti-inflammation and inhibition of bacterial virulence. CONLUTSION Macrolide drugs are effective in treatment of bronchitis, cystic fibrosis (CF), bronchiectasis, chronic paranasal sinusitis (CPS), burn complications of PA.