Trimetazidine is widely used in the treatment of stable coronary artery disease (CAD) and its cytoprotective effect has been confirmed in animal studies and in many clinical trials. Given the inflammatory milieu of CAD and trimetazidine effect on the inflow of neutrophilis to the ischemic area, it is interesting to consider whether trimetazidine actions could be also explained through the inhibition of inflammatory mediators, including cytokines. The aim of this study was to (i) examine the influence of treadmill exercise test (TET) on serum C-reactive protein (CRP) and interleukin-6 (IL-6), and (ii) the influence of three-month trimetazidine therapy on serum CRP and IL-6 concentrations. One hundred and fifty-six patients with stable CAD were included. TET was performed (according to the standard Bruce protocol) twice for all subjects at baseline and after the three-month trimetazidine treatment. Serum IL-6 and CRP concentrations were determined prior to and after performing each TET. Exercise led to the increase of CRP (2.35 vs 2.81 mg/L, p<0.05) and IL-6 concentrations (1.64 vs 1.92 pg/ml, p=0.0318) in patients without trimetazidine. Three-month treatment resulted in the increase in the TET duration (378.0s vs 410.9s, p<0.05) and decrease in serum CRP concentration, both before (2.35 vs 1.51 mg/L, p<0.05) and after TET (2.81 vs 1.69 mg/L, p<0.05). There was no significant increase of CRP after the second TET (1.51 vs 1.69 mg/l, p=NS). Three-month trimetazidine treatment increased IL-6 concentrations (1.64 vs 2.23 pg/mL, p<0.05). TET was not associated with further changes in IL-6 concentrations (2.23 vs 2.18 pg/mL, p=NS). Serum IL-6 and CRP concentrations increase during exercise in patients without trimetazidine. Three-month trimetazidine prolonged the duration of TET. Moreover, it resulted in the reduction of CRP concentration The increase of IL-6 concentration after three-month trimetazidine treatment and the lack of changes of its concentration after TET is associated with yet another mechanism of trimetazidine.