Abstract: Objective To observe the effect of recombinant human endostatin （endostar） in combination with radiation on hepatic carcinoma xenografts in mice under different timing of administration，endostar dose and radiation dose. Methods（1）The xenotransplanted tumor model of human hepatic carcinoma in mice was established. The mice were randomly grouped based on timing of administration，endostar dose and radiation dose, with 10 mice in each group. The length and diameter of xenografts were measured every other day. The tumor suppress effect was compared between early administration and late administration manners.（2）The mice were divided into 6 groups with 30 mice in each group and treated in early administration manner. Then the overall survival was observed.（3）MTT assay was used to observe the synergistic effect influenced by the dose of endostar and radiation.（4）Western blotting was used to detect the expression of epidermal growth factor （EGF）and vascular endothelial growth factor receptor-1（Flt-1）in early and late administration manners.（5）Immunochemistry was used to test the expression of vascular endothelial growth factor（VEGF）and KDR，as well as microvascular density of hepatic carcinoma xenografts.（6）Cyto-apoptosis was observed by electron microscope and cell cycles and apoptotic rates were determined by flow cytometry. Results Compared with control group，endostar could suppress the growth of hepatic carcinoma xenografts（P＜0.05），and early administration manner performed better than late administration manner（P＜0.05）. Synergistic effect was found in 8 mg／kg endostar+RT group of early administration manner，and the tumor suppress rate was 58.0％，better than other groups（P＜0.05）. The median overall survival of 8 mg/kg endostar+RT group was 55.6 days with the life prolonging rate of 29.3％，better than other groups（P＜0.05）. 5 μg／ml endostar in combination with 4Gy radiation on HUVECs cells showed synergistic effect with the proliferative inhibition rate of 59.20％，better than other doses of endostar（P＜0.05）. 200 μg／ml endostar in combination with 4 Gy radiation on HepG2 cells showed synergistic effect with the proliferative inhibition rate of 43.45％，better than other doses of endostar（P＜0.05）. 5 μg／ml endostar in combination with different doses of radiation on HUVECs，as well as 200 μg／ml endostar in combination with different doses of radiation on HepG2 cells both showed better proliferative inhibition rates than using endostar or radiation alone（P＜0.05）. Western blotting test showed that the expressions of EGF in 8 mg／kg endostar group and 8 mg／kg endostar+RT group of early administration manner was lower than those of late administration manner. However，the expression of Flt-1 between the two manners had no difference（P＞0.05）. Endostar in combination with radiation could significantly decrease MVD of hepatic carcinoma xenografts，the MVD in 8 mg／kg endostar+RT group was 8.6±1.3，lower than other groups（P＜0.05）. In 8 mg／kg endostar+RT group，the expression of VEGF and KDR was lower than other groups（P＜0.05）. Apoptoic changes were observed under lectron microscope in endostar in combination with radiation groups. Flow cytometry showed that cell cycles were blocked in S phase in 8 mg／kg endostar+RT group，and the cyto-apoptotic rate was higher than other groups（P＜0.05）. Conclusion The synergistic effect of endostar in combination with radiation is correlated to timing of administration，endostar dose and radiation dose，and the effect of early administration of endostar is superior to the late.