Background: Restenosis after revascularization procedures is accelerated in persons with type 2 diabetes. Aim: The current study tested the hypothesis that the neointimal response to endovascular injury is enhanced in female obese Zucker (OZ) rats, a model of type 2 diabetes. Methods: Animals were randomized to receive either a standard diet (SD) or a diabetogenic diet (DD) for 6 weeks. Four weeks later, balloon injury of the right common carotid artery was induced. All rats were euthanized 2 weeks after injury. Lean Zucker (LZ) rats served as controls. Results: At the time of death, plasma glucose was elevated in OZ rats fed a SD (208 ± 13 mg/dl) and a DD (288 ± 21 mg/dl) compared to corresponding LZ rats (SD: 153 ± 8; DD: 132 ± 7 mg/dl). The ratio of high-density lipoprotein cholesterol (HDLc) to total cholesterol (Totc), an index of atherogenicity, was reduced in OZ rats on both diets (SD: 0.77 ± 0.06; DD: 0.80 ± 0.09) compared to LZ controls (SD: 1.11 ± 0.02; DD: 1.20 ± 0.05). Histomorphometric analysis of injured arteries showed that the intima to media (I : M) ratio was significantly increased in OZ (1.37 ± 0.07) compared to LZ (0.79 ± 0.08) rats. Elevations in plasma glucose and triglycerides (Tg) correlated positively and decreases in HDLc negatively with an increased I : M ratio. Administration of the DD did not further enhance the I : M ratio in LZ (0.87 ± 0.06) or OZ (1.29 ± 0.09) rats. Conclusions: These results suggest that neointima formation following endoluminal injury of the carotid artery is enhanced at an early stage in the development of diabetes mellitus.