The pollution of heavy metals may affect the human health, in order to study the affect of heavy metals to the brain, the normal alive rabbits and the rabbits which were injected with PbCl₂ for 2 weeks were autopsied, the brain proteins were extracted and separated by gel filtration, and further analyzed by 2-D PAGE, More than one hundred water-soluble proteins of rabbit brain were visualized by Coomassie Brilliant Blue staining. The apparent molecular masses of most water-soluble proteins from rabbit brain were about 6～30 ku, pI was about 4～9. After matched with normal alive rabbit brain protein spots separated by 2D-PAGE, there obviously exists many differences displayed and unmatched protein spots in the 2-D PAGE maps of Pb²⁺ induced rabbit brain. 3 spots were extracted from the 2D-PAGE and detected by the MALDI-TOF-MS and ESI-MS, The experiments show that rabbit brain proteins would be affected by Pb²⁺ injection.