Introduction: Coronary artery disease (CAD) is the leading cause of mortality in diabetic patients. Due to the diffuse nature of their disease, diabetic patients may be at risk for incomplete revascularization, highlighting a potential role for pro-angiogenic therapy in this group. This study investigates molecular mechanisms of angiogenesis in diabetic patients. Methods: Myocardial tissue was harvested from patients undergoing coronary artery bypass grafting (non-diabetic (ND) 11, type 2 diabetic (DM) 10). Expression of angiostatin, endostatin, their precursors (plasminogen and collagen XVIII, respectively), enzymes leading to their production (Matrix Metalloprotease (MMP) 2 & 9, Cathepsin L), and an inhibitor of MMPs (TIMP2) was assessed with Western blotting. MMP activity was assessed. Coronary collateralization was graded by Rentrop scoring of angiograms. Results: Plasminogen and collagen XVIII expression were similar between groups. Angiostatin expression trended to increase 1.24-fold (p=0.07) and endostatin expression increased 2.02-fold in DM patients relative to ND (p=0.02). MMP9 expression was no different between groups, whereas MMP2 expression decreased 1.8-fold in diabetics (p=0.003). MMP2 & 9 activity decreased 1.33-fold (p=0.03) and 1.57-fold (p=0.04), respectively, in diabetic patients. Cathepsin L expression was 1.38-fold higher in diabetic patients (p=0.02). Coronary collateralization scores were ND 2.1±0.37 vs. DM 1.0±0.4 (p=0.05). Myocardial endostatin expression correlated strongly with %HbA1c (R=0.742, p=0.0001). Myocardial expression of angiostatin and endostatin demonstrated significant negative linear correlations with coronary collateralization (angiostatin R=-0.531, p=0.035, endostatin R=-0.794, p=0.0002). Conclusion: Diabetic patients with CAD exhibit increased levels of the anti-angiogenic proteins angiostatin and endostatin and differential regulation of the enzymes governing their production relative to non-diabetic patients. Myocardial levels of these proteins show significant correlation to coronary collateralization. These findings offer potential new therapeutic targets for enhancing pro-angiogenic therapy and insight in to the angiogenic impairments seen in diabetes.