Background Clinical data demonstrated that failure rate of titanium implant in irradiated bone was 2-3 times higher than that in nonirradiated bone and it is difficult to get the ideal results in irradiated bone. Purpose The aim of the study was to investigate the effects of HBO, BMP2, VEGF165, and combined use of BMP2/VEGF165 on osseointegration and stability of titanium implant in irradiated bone. Materials and Methods Sixty rabbits were randomly assigned to 5 groups (control group, HBO group, VEGF165 group, BMP2 group, and BMP2/VEGF165 group) after receiving 15 Gy radiation. Implant surgery was performed on tibias eight weeks later. They were sacrificed at two or eight weeks after operation. Implant stability, calcium, and ALP activity in serum, the ratio of bone volume to total volume, the rate of bone growth, and gene expression were assessed. Result There was no mortality and no implants failed during the experiment. Implant stability was significantly compromised in the control group compared to the other four experimental groups, and the BMP2/VEGF165 group had the highest implant stability. HBO, BMP2, and VEGF165 significantly increased BV/TV and the rate of bone growth, while the BMP2/VEGF165 showed the best effect among groups. The expression of RUNX2 in HBO, BMP2, and VEGF165/BMP2 group was higher than that in the VEGF165 and control groups at two weeks. The expression of OCN in HBO, BMP2, VEGF165, and VEGF165/BMP2 groups was higher than that in the control group, and the gene expression of CD31 was higher in HBO, VEGF165, and BMP2/VEGF165 groups than that in control and BMP2 groups. Conclusion HBO, BMP2, and VEGF165 could increase bone formation around the implant and improved the implant stability in irradiated bone. The combination use of BMP2 and VEGF165 may be promising in the treatment of implant patients with radiotherapy.