Objective: The aim of this study was to determine the level of the E3 SUMO-Protein Ligase (NSMCE2) and their relationship to Ecto-5'-nucleotidase, ADA and AMPDA enzymes in patients with atherosclerosis compared to control group. Method: Five ml of venous blood was drawn from sixty patients of atherosclerosis ranging between (40-75) years old and patients with diabetes mellitus and kidney diseases were excluded .The activity in U/L for Ecto-5'-nucleotidase, AMPDA and level of NSMCE2 (pg/ml) were measured in serum from control and patients with atherosclerosis. Results: The present study included 60 males patients with atherosclerosis and 30 matched males Original Research Article Mehdi and Jasim;AIR, 4(2): 79-86, 2015; Article no.AIR.2015.063 80 healthy individuals as control group. The present study showed that mean levels of sera Ecto-5'nucleotidase, ADA and AMPDA activities and NSMCE2 have a highly significantly increase (p<0.0001) in patients compared to control group. Conclusion: The measurement of E3 SUMO-Protein Ligase (NSMCE2) and the activates of Ecto5'-nucleotidase, ADA and AMPDA enzymes U/L in patients with atherosclerosis was highly significant elevated, compared to control group. This is normally expressed in vascular endothelial cells and in a broad range of immune cells. Therefore, adenosine formed by extracellular nucleotide catabolism on endothelial cells and immune cells appears to be an important endogenous modulator of arteriogenesis and key transcription factor involved in inflammatory responses.