BACKGROUND: Aging is a complex biological phenomenon distinguished by accumulation of deleterious changes with time including memory impairment. Physical exercise positively affects the brain both during aging and neurodegenerative diseases. OBJECTIVE: Studying the role of hippocampal astrocytes in the protective effect of exercise in D-galactose induced memory impairment. MATERIALS AND METHODS: Eighteen rats were divided into 3 equal groups; group I (control) was given saline i.p. for 10 weeks, group II was treated with D-galactose(D-gal 100 mg/kg i.p. for 10 weeks) as it induces memory impairment and group III was co-treated with D-gal and swimming exercise for 10 weeks. Memory and learning performance in Barnes maze test were analyzed. Brain tissue was dissected and processed for histological and immunohistochemical study using glialfibrillary acidic protein (GFAP) and induced nitric oxide synthase (iNOS) markers. Brain homogenate was prepared for estimation of malondialdehyde (MDA), superoxide dismutase (SOD), lactate and pyruvate. RESULTS: Exercise significantly improved D-gal rats' performance during acquisition and probe phases of Barnes maze test, reduced MDA and increased SOD, lactate and pyruvate levels with reduction of lactate\pyruvate ratio in brain homogenate. Neural cell count increased in hippocampus with decrease of apoptotic cells, GFAP and iNOS expression. CONCLUSION: Exercise was significantly effective in improving oxidative stress in brain and restoring hippocampal neural and astrocyte metabolic functions with resultant improvement in spatial memory performance.