This study was purposed to investigate the mechanism of low dose radiation (LDR) by proteomic technology and to find the key proteins of the hormesis and adaptive response induced LDR, which provided the foundation of experimental and theoretical basis for the clinical application of LDR. Two-dimensional electrophoresis (2-DE) was used to screen protein patterns of normal serum and serum of mice exposed to LDR in different time for qualitative and quantitative differences in protein expression. And the differentially-expressed proteins between the two groups were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). The result showed that among the differentially-expressed proteins between the group exposed to LDR and the control group (shom-irradiated group), it was found that after LDR new 4 proteins appeared, 13 proteins were up-regulated, 6 proteins were down-regulated, 3 proteins disappeared in the group exposed to LDR. In different time the quantity of some proteins was different, the protein expression had some characteristics, the estrogen receptor 2 was down-regulated, the vitamin D-binding protein and apolipoprotien were up-regulated in the group exposed to LDR. It is concluded that LDR up-regulate or down-regulate some proteins, some proteins related with LDR were found. It may provide some new explanations for the effect mechanism of the LDR.