The putative protective effects of meloxicam on the oxidative damage induced by aluminum overload in mice brain were investigated. The cerebral damage model in mice was established via intracerebroventricular (i.c.v.) microinjection of aluminum (5.0 microg in 2.0 microl), once a day for 5 days. Meloxicam, a selective inhibitor of cyclooxygenase-2 (COX-2), was intragastrically (i.g) administered 30 min before each aluminum administration, and continuously given for another 10 days after the last aluminum administration. Behavioral changes including locomotor activity, passive avoidance, and spatial learning and memory ability were examined two weeks after the last administration of meloxicam. To determine the brain damage, we also measured pathological alterations in the cerebral tissue, malondialdehyde contents and expressions of Choline acetyltransferase (ChAT), amyloid precursor protein (APP) and amyloid beta. Furthermore, COX-2 proteins and COX-2 mRNA were examined to investigate the mechanism for underlying the effect of meloxicam. The impairment of learning and memory function was caused by aluminum overload. Consistent with the behavioral changes, neuronal death in the hippocampi, increased content of malondialdehyde, expressions of APP, amyloid beta and COX-2 proteins, as well as COX-2 mRNA, and decreased expression of ChAT protein were detected in the aluminum-overload mice. Meloxicam significantly protected mice from the brain damage, and behavioral and biochemical changes above caused by aluminum overload. These experimental results indicate that there is a close relationship between over-expression of COX-2 and neuron damage induced by aluminum overload. It also suggests that selective inhibitors of COX-2 have potential values in clinical treatment for some other neuron damage-related diseases.