Abstract: Objective: To study the preventive and therapeutic effect of CEA recombinant vaccine virus (CEA-rV) on CEA-positive tumors and evaluate its safety in a clinical application. Methods: In the prevention group (group A), 40 mice were divided into 4 subgroups, which were vaccinated by subcutaneous injection (SI) with wild-type vaccinia virus (W-VV) in subgroup 1 and 2, or CEA-rV in subgroup 3 and 4 for three times at 14-day intervals. The vaccinations were then followed by SI of Hepa-CEA+ tumor cells in the 1st and 3rd subgroup or Hepa-CEA- tumor cells in the 2nd and 4th. In the treatment group (group B), 40 mice were divided into 4 subgroups, which were vaccinated by SI with Hepa-CEA- tumor cells in the 1st and 3rd subgroup or Hepa-CEA+ tumor cells in the 2nd and 4th respectively. These injections were followed by SI of W-VV in the 1st and 2nd subgroup or CEArV in the 3rd and 4th for 3 times at 14-day intervals. The animals' response was observed weekly after injection of the tumor cells in both Group A and B. In the clinical application study, 6 volunteers were vaccinated by SI with 0.5ml of CEA-rV for 3 times at 14-day intervals. The amount of serum CEA, tumor volume and the side effects were observed before and after treatment. Results: a) In Group A, the subcutaneous tumor grew rapidly at approximately the same rate (P>0.05) in all 3 control subgroups (mass about 3.5cm3 ), however, no tumor grew in the mice of the 4th subgroup in which CEA-rV and Hepa-CEA+ tumor cells were injected. B) In Group B, the subcutaneous tumors were observed in all of the control subgroups and the tumors (mass about 5cm3 ) grewquickly. In the tumors of the 4th subgroup that was injected with Hepa-CEA+ tumor cells and CEA-rV, tumors grew slowly and the tumor mass was smaller (about 1cm3) than in the other 3 subgroups, between which no statistical significant difference was found (P>0.05). The statistical difference was significant in the comparison of the fourth subgroup with the 3 control groups (P<0.01). During the testing period, no toxicity or side effects were seen in any animals of Groups A or B. The preliminary clinical results showed that CEA-rV had a fair therapeutic effect on CEA+ patients with colorectal cancer and lung adenocarcinoma. No toxicity or serious side effects were found in any patients. Conclusion: The results indicate that the CEA-rV has a preventive and therapeutic effect on CEA+ tumors. Prevention through vaccination is more effective than treatment after tumor formation, especially in patients with CEA-positive tumors. No toxicity or side effects have been found clinically.