The aim of this paper was to investigate the change of serum leptin and its relationship with platelet membrane glycoprotein Ib (GP Ib) in patients with coronary heart disease (CHD). The enrolled included 50 patients with CHD (CHD group) and 30 patients without CHD (control group) who were diagnosed by coronary angiography. The positive percentage and the average fluorescence intensity of platelet membrane GP Ib were detected by full-blood flow cytometry. Serum leptin was detected by enzyme linked immunosorbent assay. The positive percentage and the average fluorescence intensity of platelet membrane GP Ib in the CHD group were significantly lower than those in the control group (<0.05). After correcting the differences of systolic blood pressure, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting glucose, PPBS, fasting insulin and quantitative insulin sensitive index, serum leptin level in the CHD group was significantly higher than that in the control group (<0.05). Single factor correlative analysis revealed that serum leptin in CHD patients was negatively correlated with the average fluorescence intensity of platelet membrane GP Ib (<0.05). Multifactorial stepwise regression analysis showed that serum leptin in CHD patients was independently negatively correlated with the average fluorescence intensity of platelet membrane GP Ib (<0.05). Logistic analysis demonstrated that serum leptin was independently correlated with the risk of CHD (<0.05). Hyperleptinemia was verified in CHD patients. The increase of serum leptin could affect blood platelet activation. Hyperleptinemia may play an important role in the pathogenesis of CHD.