Objective To investigate the role of D-galactose, especially in the structural and functional changes of the immune system in aging. Methods Serum levels of advanced glycation end-products (AGE) were determined by ELISA method. Ultra-structures of thymus and spleen were detected by transmission electron microscopy. MTT method was used to determine the lymphocyte proliferation. IL-2 activity was determined by bioassay. Northern blot was used to detect the IL-2 mRNA levels. Results Serum AGE levels of D-galactose- (P＜0.01) and AGE-treated (P＜0.05) mice (n=8) were increased significantly. The ultra-structures of thymus and spleen in D-galactose- and AGE-treated mice showed regressive changes similar to those in the aged control group. The lymphocyte mitogenesis and IL-2 activity of spleen were also decreased significantly (P＜0.01, n=8).The change of IL-2 activity shown by Northern blot resulted from the change of mRNA expression. The AGE plus aminoguanidine group, however, showed no significant change in these parameters in comparison with the young control group (P＜0.01 or P＜0.05, n=8). Conclusion D-galactose and AGE lead to a mimic regression change of aging in the immune system in vivo.