The relationship of plasma levels of high density lipoprotein (HDL) cholesterol, apolipoproteins A-I and A-II (the major apolipoproteins in HDL), low density lipoprotein (LDL) cholesterol, triglyceride, and glucose to microangiopathy was evaluated in 49 insulin-dependent diabetic subjects. Although the HDL cholesterol/LDL cholesterol ratio (a risk determinant for macroangiopathy) was lower in women with proteinuria, no other relationships between HDL cholesterol or the A apolipoproteins and renal microangiography were found. The only independent association between HDL and retinal microangiopathy was found in women, where an inverse correlation was found between the apo A-I/apo A-II ratio and the number of microaneurysms (rs = −0.561, P < 0.05). Men showed strong relationships of glucose, triglyceride, cholesterol, and LDL cholesterol to renal microangiopathy whereas women, in general, had stronger correlations of these variables with retinal microangiopathy. Thus, several alterations in lipoprotein cholesterol distribution and HDL composition are associated with diabetic microangiopathy. In addition, differences between sexes suggest that previously undescribed hormonal factors may influence the severity of this process.