Repetitive transcranial magnetic stimulation (rTMS) is a rapidly expanding mean in drug resistant depression treatment. Yet, despite vast research in this field, exact neurophysiological mechanism of rTMS therapy still remains unclear. This results in difficulties choosing suitable rTMS parameters in advance and compromises thorough evaluation of efficacy after the treatment. In order to obtain more explicit assessment of rTMS therapy in the psychiatric field, we evaluated and compared the influence of two most widely used antidepressive rTMS protocols on EEG band power spectrum and relation to clinical test scores (MADRS, BDI, HAM-D17). Forty-five patients (12 male, 33 female, mean age 52.16 years) participated in the study. Twenty-three patients received high frequency (10 Hz) stimulation, the rest 22 were stimulated using low frequency (1 Hz) protocol. Both groups received 10 to 15 daily rTMS sessions. EEG recordings and clinical tests were obtained the day before rTMS course and same day after the last session. Majority (57.78%) of patients showed considerable improvement after the treatment. There were no notable differences in clinical test score drop between the two rTMS protocols. However, we found that different protocols resulted in significantly different electrophysiological changes. High frequency (10 Hz) rTMS resulted in widespread changes off EEG band power, including delta power increase on the left hemisphere and alpha power growth on the right. Theta power increase was also obtained in parietal-occipital areas. Low frequency (1 Hz) rTMS showed to have no major effect on basic EEG band power, however, we found a notable shift of frontal alpha power asymmetry towards the right hemisphere, which correlated with the clinical outcome. Our study results suggest that two widely used rTMS protocols strongly differ in their electrophysiological mechanisms. Low frequency stimulation finesse on frontal alpha power asymmetry shift, whereas high frequency protocol acts on wider electrophysiological changes in the brain.