To explore the protective effect of tetramethylpyrazine （TMP） on the learning and memory function in D-galactose （D-gal）-lesioned mice. Methods C57BL/6 mice were injected （s.c.） 2% D-gal for 40 days （100 mg·kg-1·d-1）. Normal saline

TMP

and Huper-zine A were respectively given by intragastric administration in different groups from the third week. Learning and memory ability was tested with Morris water maze for 5 days at the sixth week. After completion of behavioral test

the mice were sacrificed by decapitation. The brain was rapidly removed

and the cortex and hippocampus were separated. The superoxide dismutase （SOD） activity and malondialdehyde （MDA） content in the cortex were determined. At the same time

the activity of choline acetyltransferase （ChAT） and acetylcholinesterase （AChE）

the binding sites （Bmax） and the affinity （KD） of M-cholinergic receptor in the cortex

and Bmax and KD of N-methyl-D-aspartate （NMDA） receptor in the hippocampus were determined. Results In this model group

（1） The deficit of learning and memory ability

（2） elevated MDA content and lowered SOD activity

（3） decreased AChE activity and M-cholinergic receptor binding sites in the cortex

and （4） lowered NMDA receptor binding sites were observed in the hippocampus

as compared with the normal control. TMP could markedly （1） attenuate cognitive dysfunction

（2） lower MDA content and elevate SOD activity

（3） increase the activity of ChAT and AChE

and M-cholinergic receptor binding sites in the cortex in the mice treated with D-gal. NMDA receptor binding sites were also increased in the hippocampus in the treated mice. Conclusion TMP can significantly strengthen antioxidative function

improve central cholinergic system function

protect NMDA receptor activity

and thus enhance the learning and memory ability in D-gal-lesioned mice.