We examined the effect of Hippophae rhamnoides L. (HRL) juice on lead-induced memory impairment and neuronal damage in the brains of adult mice. Kunming mice were exposed to lead acetate 10 mg/kg body weight for 20 d. Twenty percent and 40% HRL prevented the lead-induced decrease in step-through latency. In the water maze test, the swimming time was lengthened in mice treated with lead acetate, but this time was decreased in mice that received 20% and 40% HRL. The malondialdehyde (MDA) levels were increased in lead-treated mice, which were reduced by 20% and 40% HRL in dose-dependent manner. The activities of acetylcholinesterase (AchE) and monoamine oxidase-A and -B were significantly increased in the lead-treated group, which were decreased by 40% HRL but not by 20% HRL. The levels of norepinephrine, serotonin, and 5-hydroxyindole acetic acid were decreased significantly in the lead-treated mice, and the decreases were antagonized by 40% HRL, except for than in dopamine, but 20% HRL had no effect on this change. These data suggest that the different doses of the HRL juice protect against the lead acetate-induced deficits in learning and memory and changes in neurobiochemical parameters.