Diabetic nephropathy (DN) is a major cause of sickness and death in people with diabetes. It can lead to the need for dialysis or a kidney transplant. Ca+2 / Mg+2ATPase is an important regulator of intracellular calcium concentration and therefore, of erythrocyte deformability. So the present study was aimed to evaluate the erythrocyte Ca+2 / Mg+2ATPase activity in type 2 diabetes patients and reveal any associations between enzyme activity and diabetic nephropathy. The study included sixty patients with type 2 diabetes who were subdivided into thirty with nephropathy (microalbuminuria and macroalbuminuria) and thirty without complications. Twenty healthy subjects, age- and sex- matched were included as control group. Patients and controls were assessed for FBG, PBG, glycosylated hemoglobin (HbA1c), serum creatinine and urea levels, lipid profile and fasting C-peptide level, microalbuminuria and Ca+2 / Mg+2ATPase activity. The results showed that a significant decrease in Fasting C-Peptide of patients with diabetic nephropathy group as either compared with diabetic without complication or control group. Moreover there was a significant decrease in Ca+2/Mg+2 ATPase activity among patients with type 2 diabetes and with or without nephropathy as compared with control group. Also enzyme activity did not differ among the degrees of nephropathy. Thus, alteration of Ca+2/Mg+2 ATPase activity and Fasting C-Peptide may be recognized features of Type 2 diabetes mellitus.