DIPYRIDAMOLE (DP), a pyrimido-pyrimidinic derivative is a phosphodiesterase inhibitor, chemically related to adenosine and inhibits the cellular uptake of adenosine with antithrombotic and vasodilation actions. The aim of this study is to evaluate the effect of subcutaneous administration of DP (100 mg/ kg body wt, 5 times/ week for 3 weeks) on oxidative stress in 6 Gy γ-irradiated rats delivered at a single dose. Irradiated group revealed significant increase of serum malondialdehyde (MDA), advanced protein oxidation products (AOPP), protein carbonyl (PCO), nitric oxide (NO), urea, triglycerides and cholesterol contents. While, there was a significant decrease of blood reduced glutathione (GSH), erythrocytes (RBCs) and platelets counts, haemoglobin content (Hb), haemotocrit value (Hct), count of total leukocytes, neutrophils and lymphocytes. Irradiated DP treated rats showed significant improvement in the radiation-induced disorders in all tested parameters. The current study highlights DP as promising agent which could strengthen the defence mechanisms of the physiological systems against the oxidative stress induced by ionising irradiation.