Leptin has been reported to exert an atherosclerotic effect by regulating expression of angiogenic factors that have been implicated in the pathogenesis of coronary artery disease (CAD). The purpose of this study was to investigate whether lipid-lowering therapy (LLT) with statins could affect leptin levels and angiogenic factors in patients with CAD. This study included 76 patients with CAD and 15 subjects without CAD (non-CAD). CAD patients were randomized to 6 months of intensive LLT with atorvastatin or moderate LLT with pravastatin. Plasma leptin, angiopoetin-2 (Ang-2), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels were measured prior to statin therapy (baseline) and after 6 months. Baseline levels of leptin, Ang-2, HGF and VEGF were higher in the CAD group than in the non-CAD group (all P < 0.05). Treatment with intensive LLT decreased leptin, Ang-2, HGF and VEGF levels, whereas moderate LLT did not change these levels. This study suggests that LLT with atorvastatin decreases leptin levels and angiogenic factors in patients with CAD, possibly contributing to the beneficial effects of LLT with atorvastatin in CAD.