Treatment-resistant depression (TRD) is a challenging issue to address. Repetitive transcranial magnetic stimulation (rTMS) is commonly used but shows varying efficacy, necessitating a deeper understanding of depression physiology and rTMS mechanisms. Notably, an increasing amount of recent data has displayed the connection of TRD and its clinical outcome with chronic inflammatory processes. The current study included 19 TRD patients undergoing rTMS and 11 depressed patients responding to medication as a comparison group. We assessed therapeutic efficacy using MADRS, HAM-D-17, GAD-7, and PHQ-9 tests. Inflammatory markers, neurotrophins, and associated miRNAs were measured in patients blood serum before and during treatment. A control group of 18 healthy individuals provided baseline data. The results of our study showed significantly higher levels of pro-inflammatory interleukins-6 and − 8 in TRD patients compared to drug-responders, which also related to more severe symptoms before treatment. In addition, TRD patients, both before and during treatment, exhibited higher average blood serum concentrations of pro-inflammatory interleukin-18 and lower levels of anti-neuroinflammatory miR-146a-5p compared to healthy controls. We also observed that the expression of miR-16-5p, miR-93-5p, and especially miR-146a-5p correlated with clinical changes following rTMS. Our study confirmed that TRD patients possess a higher inflammatory status, while the anti-neuroinflammatory miR-146a-5p was demonstrated to have a considerable potential for predicting their rTMS treatment success.