Background. One of the mechanisms of P.aeruginosa resistance to antimicrobial agents (AMAs) is the hyperactivity of efflux pumps, particularly MexAB-OprM and MexXY of the RND family, which are the determinants of resistance to aminoglycosides, fluoroquinolones and others [1]. It is known that drugs capable of affecting quorum sensing systems, in particular macrolides, can reduce P.aeruginosa resistance to host defense mechanisms [2], which may increase the susceptibility of this pathogen to AMAs. Aim. To determine the expression of efflux pump genes mexR, mexY, and oprM in P.aeruginosa under the influence of azithromycin and clarithromycin. Methods. Expression of the mexR, mexY and oprM genes in P.aeruginosa 449 at 0.5 MIC of azithromycin (25 μg/ml) and clarithromycin (100 μg/ml) was determined by RT-qPCR using SYBR Green dye. Amplification was performed under the following thermal cycling conditions: 20 s at 95 °C, followed by 40 cycles of 15 s at 95 °C and 60 s at 60 °C. The endogenous control was 16S rRNA gene. Statistical analysis of the results was carried out using the ANOVA method. Results. According to the obtained data, under the action of azithromycin the transcriptional activity of the mexR, mexY and oprM genes in the clinical isolate P.aeruginosa 449 decreased 3.2-fold, 7.8-fold and 5.3-fold, respectively. Under the influence of clarithromycin an increase in the expression of mexR and mexY genes was observed, by 1.6-fold and 7.8-fold, respectively, while the expression of the oprM gene decreased 2.8-fold compared to the control (p < 0.05). Conclusions. Thus, second — generation macrolide antibiotics azithromycin and clarithromycin affect the transport systems of P.aeruginosa. The decrease in the expression of mexY and oprM genes under azithromycin exposure may contribute to increased susceptibility of P.aeruginosa to aminoglycosides. Under the influence of clarithromycin activation of the mexR and mexY genes was observed, which may lead to the development of multidrug resistance, biofilm formation with chronic inflammation and alterations of P.aeruginosa virulence.