Introduction: One of the most frequently occurring macro vascular complications is cardiovascular disease (CVD). It is a leading cause of morbidity and mortality in many countries worldwide and is estimated that it will be the single largest cause of disease burden globally by the year 2020. Diabetes mellitus (DM) is found to be the major risk factor for cardiovascular disease (CVD). As compared with individuals without diabetes, CVD is 2–4 times more common in people with diabetes and is associated with a higher mortality. Objective: The main objective of the present study is to observe the association of CVD with type 2 diabetes and genetic markers such as plasma proteins namely, Haptoglobin [HP], Group specific component [GC], Transferrin [TF], Albumin [ALB] and Caeruloplasmin [CP] systems. Materials and Methods: In the present study, fifty cases presenting cardio vascular disease with type 2 diabetes mellitus and fifty cases of age and sex matched healthy controls were included. Plasma samples were typed using PAGE electrophoresis. The statistical significance of differences between patients and controls were tested. Analysis of the data was carried out using Epi Info 5 software. Relative risk was calculated by the random-effects method. Results: The study was observed that in the case of CVD with diabetes type 2 patients were showing significant association for HP (χ2:6.2864; d.f.= 2;0.05>p>0.02) and GC (χ2:10.0150; d.f.= 2; 0.01> p> 0.001) systems. Risk estimates showed a significant association of HP 2-2 and GC 2-1 phenotypes with CVD-type 2 diabetes mellitus individuals (RR = 2.23). The result shows an increased risk of 100% and more, indicating that individuals with these phenotypes were two times more likely to get the disease when compared with the other phenotypes of the HP and GC systems.