Background: The neurodegenerative changes occurring during aging is associated with oxidative stress and inflammatory responses. The role of induction or suppression of heme-oxygenase-1 (HO-l) in these changes still a mystery. Aim: This study was designed to investigate the effect of hemoxygenase-1 (HO-1) induction and suppression on lipopolysaccharide- brain injury in male rats. Materials and Methods: Forty male albino rats were divided into four equal groups: a) control group, received saline at a dose of 10 ml/kg, intraperitoneally (IP) for 2 weeks; b) LPS group, received LPS (5mg/kg/day) IP for 2 weeks; c) Hemin group, received Heminat a dose of 15 mg/kg/day IP along withLPS for 2 weeks; d) Nimodipine group, received Nimodipineat a dose of 30 mg/kg/day IP along with LPS for 2 weeks.At the end of the experimental period, all animals were tested for cognitive tests (two-way active avoidance test). Then, the animals were sacrificed by decapitation. Brains of experimental groups were harvested for measurement of HO-1,NO, BDNF, Glu, MDA levels and CAT activity. Results: LPSsignificantly decreasedavoidance number in a 10 block trials and significantly increased the highest avoidance latencies, associated with a significant decrease in BDNF, GLU levels & CAT activity, and a significant increase in brain HO-1, NO, MDA levels compared to control group. Treatment with Hemin deteriorated all these parameters and treatment with Nimodipinesignificantly improved all these parameters. Conclusion: Suppression of HO-1 by Nimodipinecan have a beneficial effect on neurodegenerative changes associated with aging.