Objective To study the effect of experimental lead exposure on NOS in the rat hippocampus and cerebral cortex,and explore the neurotoxic mechanism of lead on CNS. Methods Four weeks old male Wistar rats were exposed to lead by intragastric administration with 45mg/kg.bw lead acetate 30 days.On the 30th day,the activity of total NOS and iNOS enzyme in hippocampus and cerebral cortex was determined.the β-NADPH histochemical method was used to study nNOS of hippocampus of rat.Results Compared with black group,the activity of total NOS enzyme was dramatically suppressed in both hippocampus and cerebral cortex,but the activity of iNOS was dramatically increased,and the number of masculine nNOS was dramatically suppressed in CA1 and gyrus of hippocampus in experimental group.Conclusion the enzyme activity of NOS in the rat hippocampus and cerebral cortex could be decreased by lead exposure,but iNOS could be increased.The number of masculine nNOS was suppressed in hippocampus by lead exposure.