Mammalian paraoxonases (PONs) are a group of enzymes of calcium-dependent, esterases consisting of Paraoxonase-1, 2 and 3 Paraoxonase. But, PON1 has the dominant PON activity in blood. It is synthesized by the liver and found in the circulation associated with high-density lipoproteins (HDL). It protects low density lipoprotein (LDL) and HDL from lipid peroxidation. Alterations in circulating PON1 level have been reported in a variety of diseases involving oxidative stress including non-insulin dependent diabetes mellitus (NIDDM) and ischemic heart disease (IHD). The aim of this work has been planned to demonstrate PON1 activity in different diseases associated with dyslipidemia as NIDDM and IHD. This study was carried out on 20 Patients with NIDDM (NIDDM group) and 20 patients admitted to the Cardiac Care Unite with IHD (IHD group) in addition to 20 healthy subjects free from any disease as control group. All groups were selected from Suez Canal University Hospital. They were subjected to full history tacking and assay of fasting blood sugar, lipid profile and liver function tests using colorimetric methods. In addition, PON1 activity was measured using paraoxon as a substrat and apolipoprotein A1 (ApoA1) was measured using nephlometric method.Our results showed that patients with NIDDM and IHD had higher BMI, they were dyslipidemic where cholesterol, triglycerides and low density lipoprotein were higher and HDL was lower in the two patients groups compared to the control. In addition PON1 activity and ApoA1 were decreased in the two patients groups compared to the control. A positive correlation was found between PON1 and ApoA1 in the two patient's groups.Conclusions: PON1 activity and ApoA1 were reduced in Diabetes mellitus and Ischemic heart disease patients compared to the controls. Dyslipidemia is associated with patients of mentioned diseases with higher body mass index.