Abstract: It is well known that the infectious diseases caused by virus and bacterium frequently occur in one year and two years old grass carp but rarely in the three years old grass carp.This phenomenon suggests that the grass carp can establish the ability to resist the virus and bacterium by itself.However, some genes that are interrelated to the immune system would not be expressed and the grass carp would not complete the immune system until develop for more than two years.To determine the developmental genetic cause of different disease-resistant ability in grass carp of various developmental stages, we investigated the proteomic di-f ference between kidneys of one year and two years old grass carp with methods of proteomics.The kidney of fish contains pronephros and mesonephros.The main function of the pronephros is immunity, and the mesonephros can produce blood cells including the leukocytes and erythrocytes that are also associated with immunity.Therefore, the whole kidney rather than head kidney was utilized for proteomic experiment to reflect the developmental genetic backgrounds.After extraction, the total kidney proteins both one year old and three years old grass carp were separated by two-dimensional polyacrylamide gel electrophoresis.The silver stained gel images were analyzed with PDQUST software and about 900 protein spots were determined.Most protein spots were distributed in the gel area of pH4.5-7 and Mr 6612kDa.23 differential protein spots were detected.Among them, 3 protein spots were observed only in three years old grass carp, and other 20 spots were up-or down-regulated protein.Four differential proteins were identified by matrix assisted laser desorption /ionisation-time of fligh-t mass spectrometry and database analysis.These proteins are Novel Protein Similar to Novel Immune-Type Receptors 2, Recombination Activating Gene 1, MHC Class ? Beta Chain andWnt4.The preceding three proteins are directly associated with the immunity and the forth protein is associated with the kidney development.Since these identified proteins are not the antibody proteins that are induced by antigens but the proteins that have something to do with the development of the immune system or kidney, they might play a role in perfection of the disease-resistant system of the three years old grass carp.These results suggested that the different disease-resistant ability in various developmental stages of grass carp might have its developmental genetic cause.