Several studies have shown that diabetes mellitus increases the risk of restenosis after coronary intervention, but the role of insulin in restenosis has not been defined. The relation between fasting insulin levels and restenosis was evaluated prospectively at 6-month angiographic follow-up in 70 patients undergoing excimer laser coronary angioplasty of 75 lesions. Restenosis (> 50% diameter narrowing on quantitative angiography) was observed at 37 of 75 treated sites (49%). Although patients with glucose intolerance and noninsulin-dependent diabetes mellitus showed a trend toward increased restenosis (restenosis rate 69%; odds ratio for restenosis 2.7 [95% confidence interval 0.76, 9.82]; p = 0.124), those with increased fasting insulin levels > 15 muU/ml had reduced restenosis (restenosis rate 24%; odds ratio 0.22 [0.07, 0.67]; p = 0.008). Other factors including fasting serum glucose, glycated hemoglobin and lipoprotein fraction were not predictive of restenosis. The relation between insulin levels and restenosis after excimer laser angioplasty may provide insights into the biology of vascular injury and repair after coronary intervention.