Emerging evidence that the cannabinoid type 1 receptor (CB1) and its endogenous ligands, endocannabinoids, involved in regulation of feeding behavior and body weight. Over-activation of ECS is associated with metabolic diseases as dyslipidemia and insulin resistance involved in CAD and diabetes. The aim was to determine whether G1359A polymorphism of CNR1 associated with CAD with and without T2DM, and with T2DM patients free of CAD and elucidate the association of CNR1 polymorphism with CAD risk factors. The study was carried on 50 patients with CAD (25 patients with and 25 patients without T2DM), 25 patients with T2DM free of CAD and a group of 20 healthy subjects as a control group. Coronary artery angiography for patient group, serum lipid profile (TG, TC, LDL and HDL) and assessment of G1359A polymorphism of CNR1 by RFLP method were done. CAD patients with and without T2DM had significantly higher age, fasting blood glucose, systolic and diastolic blood pressure, male gender, smoking, and body mass index (BMI) compared with control. GG genotype and G allele of G1359A polymorphism were significantly associated with CAD patients with T2DM (p<0.05). G allele increased risk of occurrence of CAD with diabetes by 5.22 (OR) 95% CI (1.32-20.54). GG genotype was significantly associated with higher TC (p<0.01), LDLc (p<0.001) and BMI (p=0.001). Association of G1359A polymorphism with BMI and disordered lipid may explain in part its association with CAD patients with T2DM and may encourage use of cannabinoid receptor antagonist in treatment of these disorders.