Aim To study the mechanisms of the high restenosis rate of the patients with diabetes mellitus after percutaneous transluminal coronary angioplasty (PTCA) and the influence of L-arginine (L-Arg) and vitamin C (Vit C) on intimal hyperplasia. [WT5”HZ]Methods The iliac arteries of 36 diabetic rabbits induced by alloxan and 8 normal rabbits were injured by balloon. All rabbits were divided randomly into control group, DM group, L-Arg group, Vit C group and L-Arg+Vit C group, respectively provided with normal drinking water, normal drinking water, 2.25% L-Arg solution as the drinking water, Vit C (0.25 mg/g·d), or combided L-Arg with Vit C for 5 weeks. 4 weeks after the balloon injury, all the illacs were excised to being analyzed by computer after formaldehyde-intu-perfuse. Results The neointimal area of DM group was significantly larger than that of control group (0.255±0.024 mm 2 vs 0.176±0.029 mm 2,P<0.01), however, the neointimal area of L-Arg+Vit C group was significantly reduced than that of DM group (0.153±0.016 mm 2 vs 0.255±0.024 mm 2,P<0.01), together with a significant decrease in malondialdehyde (MDA) plasma level and significant increase in both superoxide dismutase (SOD) and nitric oxide (NO) plasma levels than those of DM group. Conclusions The therapy of combining L-Arg with Vit C could reduced the neointimal hyperplasia induced by balloon injury in diabetic rabbits. It might be effective by increasing the synthesis of endothelium-derived relaxing factor (EDRF) and protecting EDRF from being quenched by oxygen free radical.