Purpose To evaluate the efficacy of intraarterial infusion of CO 2-saturated solution in rabbit VX2 thigh tumors. Materials and Methods Fourteen Japanese white rabbits had VX2 tumors implanted in the right femoral muscle 3 weeks before intraarterial infusion. Rabbits were divided into control and CO2 groups (n = 7 each). Fifty milliliters of solution (saline solution and CO2-saturated solution for the control and CO2 groups, respectively) was administered via a 24-gauge catheter in the ipsilateral iliac artery close to the feeding artery of the VX2 tumor. All rabbits were killed for tumor harvest on day 3 after the procedure. Tumor volume was evaluated with in vivo direct caliper measurement and contrast-enhanced computed tomography (CT). Tumor apoptotic changes were examined by DNA fragmentation assay and immunoblot analysis. The tumor growth ratio and apoptotic cell rate were analyzed. Results Body weight was equally increased in both groups, but the mean tumor growth ratio was significantly decreased in the CO2 group compared with the control group (-9.5% ± 7.9 vs 27.2% ± 6.6 and 4.1% ± 4.4 vs 35.7% ± 4.5 measured by calipers and contrast-enhanced CT, respectively; P <.01). Apoptotic activity in the CO2 group was higher than in the control group (number of apoptotic cells per area, 215.0 ± 58.7 vs 21.8 ± 5.4; adjusted relative density of cleaved caspase-3, 0.23 ± 0.07 vs 0.04 ± 0.01; P <.01). Conclusions Intraarterial infusion of CO2-saturated solution inhibits rabbit VX2 thigh tumor growth by activation of apoptotic cell death through cleaved caspase-3 upregulation.