Abstract: Exposure to γ-radiation and/or lead causes numerous malfunctions in the brain. The present study was performed to investigate the possible protective effect of ginkgo biloba extract in ameliorating the biochemical changes induced in brain of rats by single exposure to 6Gy whole body γ-radiation and/or i.p. administration of lead acetate (25 mg/kg) daily for seven days. Ginkgo was orally administered in two dose levels 50 and 100 mg/kg for 7 successive days. Animals were classified into 10 groups: control, 6Gy irradiated, lead-treated, irradiated lead-treated, irradiated treated by ginkgo extract in both dose levels, lead-treated receiving ginkgo in both dose levels and irradiated lead-treated receiving ginkgo in both dose levels. Radiation and/or lead acetate increased brain oxidative stress biomarkers manifested by increased brain contents of lipid peroxides and nitric oxide parallel to depletion of reduced glutathione. In addition, brain dopamine (DA) content and lactate dehydrogenase (LDH) activity increased; whereas cholinesterase (ChE) activity decreased. Furthermore, both toxicants increased brain contents of calcium and zinc; meanwhile iron content was decreased. Administration of ginkgo biloba, in both dose levels effectively alleviated radiation- and lead-induced brain oxidative stress and restored the activities of LDH and ChE enzymes. In addition, ginkgo corrected the metabolic disturbances induced in brain by radiation and lead as reflected by lowering of DA, calcium and zinc contents parallel to increased iron content. In conclusion, ginkgo biloba extract can protect the brain against the hazards of exposure to γ-radiation and/or lead.