Purpose/Objective: Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by smooth muscle cell proliferation. This study examined the effects of external beam irradiation on neointimal proliferation after external injury to the central artery of the rabbit ear.Materials & Methods: 40 male New Zealand White rabbits were used in this study. Crush lesions were performed on each ear under general anesthesia and bilateral auricular nerve blockade. A single dose of 12 Gy (n=10), 16 Gy (n=10), or 20 Gy (n=10) and a fractionated dose of 4 5 Gy (n=10) gamma radiation was delivered to the left or right central artery of the ear 24 hours after injury; the contralateral central artery served as control. All rabbits were sacrificed after twenty-one days and the central arteries of the ear were fixed for morphometric measurements.Results: Mean (± SD) neointimal area was 0.062 ± 0.005 mm 2 (12 Gy), 0.022 ± 0,005 mm 2 (16 Gy), 0,028 ± 0,006 mm 2 and 0.038 mm 2 ± 0,02 mm 2 (4 5 Gy) in irradiated arteries compared with 0,081 ± 0,009 mm 2 in the control group. Mean (±SD) luminal area was 0.049 ± 0.004 mm 2 (12 Gy), 0.059 ± 0.002 mm 2 (16 Gy), 0.072 ± 0,006 mm 2 (20 Gy) and 0.048 mm 2 ± 0,018 mm 2 (4 5 Gy) in irradiated arteries compared with 0,043 ± 0,008 mm 2 in the control group. The difference in neointimal and luminal area between control and irradiated arteries was significant (p<0.05) only for the 16 and 20 Gy group compared to control.Conclusion: We conclude that in this model, external beam X-ray irradiation was successful in reducing neointimal proliferation after injury of the central artery of the rabbit ear. The optimal dose seems to be a single dose of 16 Gy - 20 Gy. Only a less prominent effect was noted for a fractionated dose of 4 5 Gy. Whether this approach can be used successfully to inhibit restenosis in the clinical setting requires further investigation.