The aim of the present study was to assess the impact of combined therapy with rosuvastatin (10 mg/kg) and amitriptyline (10 mg/kg) on oxidation-reduction status in the blood of rats. After 2-week application of drugs alone or their combination, the activity of glutathione peroxidase (GPX), glutathione reductase (GR) and total antioxidant status (TAS) were determined. It was noticed that combined therapy with rosuvastatin and amitriptyline significantly increased the activity of GPX in comparison to the group receiving only rosuvastatin and decreased the activity of GR in comparison to groups receiving only rosuvastatin or amitriptyline. However, the activity of these enzymes as a result of combined therapy was placed in the level of the control groups. Our studies indicated that the combined therapy with both drugs caused an increase of TAS compared to the groups of animals receiving only one of these drugs. The results indicate on the oxidation-reduction balance and increasing the antioxidant status in rats treated with rosuvastatin and amitriptyline.