We have investigated radiation-sensitive expressed genes (EGs), their signal pathways, and the effects of ionizing radiation in the thymus of ICR and AKR/J mice. Whole-body and relative thymus weights were taken and microarray analyses were done on the thymuses of high-dose-rate (HDR, 137Cs, 0.8 Gy/min, a single dose of 4.5 Gy) and low-dose-rate (LDR, 137Cs, 0.7 mGy/h, a cumulative dose of 1.7 Gy) irradiated ICR and AKR/J mice. Gene expression patterns were validated by quantitative polymerase chain reaction (qPCR). The effect of ionizing radiation on thymus cell apoptosis was measured terminal deoxynucleotidyl-transferase-mediated dUTP-end labeling (TUNEL). LDR-irradiation increased the mean whole-body weight, but decreased the relative thymus weight of AKR/J mice. Radiation-sensitive EGs were found by comparing HDR- and LDR-irradiated ICR and AKR/J mice. qPCR analysis showed that 12 EGs had dose and dose-rate dependent expression patterns. Gene-network analysis indicated that Ighg, Igh-VJ558, Defb6, Reg3g, and Saa2 may be involved in the immune response, leukocyte migration, and apoptosis. Our data suggest that expression of the HDR (Glut1, Glut4, and PKLR) and LDR radiation-response genes (Ighg and Igh-VJ558) can be dose or dose-rate dependent. There was an increased number of apoptotic cells in HDR-irradiated ICR mice and LDR-irradiated AKR/J mice. Thus, changes of the mean whole-body weight and relative thymus weight, EGs, signal pathways, and the effects of ionizing radiation on the thymus of ICR and AKR/J mice are described.