Taken into consideration that oxidative stress response after preconditioning with phosphodiesterase inhibitors (PDEIs) and moderate physical activity has still not been clarified, the aim of this study was to assess the effects of PDEIs alone or in combination with physical activity, on systemic redox status. The study was carried out on 96 maleWistar albinorats classified into two groups. The first group included animals exposed only to pharmacological preconditioning (PreC) maneuver (sedentary control (CTRL, 1 ml/day saline,n=12), nicardipine (6 mg/kg/day of NIC,n=12), vinpocetine (10 mg/kg/day of VIN,n=12), and nimodipine (NIM 10 mg/kg/day of,n=12). The second included animals exposed to preconditioning with moderate-intensity training (MIT) on treadmill for 8 weeks. After 5 weeks from the start of training, the animals were divided into four subgroups depending on the medication to be used for pharmacological PreC: moderate-intensity training (MIT+ 1 ml/day saline,n=12), nicardipine (MIT+ 6 mg/kg/day of NIC,n=12), vinpocetine (MIT+ 10 mg/kg/day of VIN,n=12), and nimodipine (MIT+ 10 mg/kg/day of NIM,n=12). After three weeks of pharmacological preconditioning, the animals were sacrificed. The following oxidative stress parameters were measured spectrophotometrically: nitrites (NO₂⁻), superoxide anion radical (O₂⁻), hydrogen peroxide (H₂O₂), index of lipid peroxidation (TBARS), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). Our results showed that PDE1 and MIT preconditioning decreased the release of prooxidants and improved the activity of antioxidant enzymes thus preventing systemic oxidative stress.