In patients with insulin-dependent diabetes mellitus (IDDM), albuminuria reflects widespread vascular dysfunction. Albuminuria has been associated to defects of heparan sulfate proteoglycan (HSPG) within the extracellular matrix. Our hypothesis is that loss of HSPG in vascular walls reduces the HSPG-bound lipoprotein-lipase activity (LPLA), thereby causing elevated levels of plasma triglyceride (TG) seen in IDDM patients with albuminuria. The aim of the present study was to evaluate whether LPLA in muscle capillaries could be related to TG in IDDM patients with and without albuminuria. This is a cross-sectional study including ten healthy control subjects (group C), nine patients with IDDM and urinary albumin excretion rate (AER) of 30 mg/24 h or less (group D0) and 20 patients with IDDM and AER greater than 30 mg/24 h (group DA). Muscle LPLA, plasma TG, total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and very-low-density lipoprotein cholesterol (VLDL) were measured. Between groups no difference in total cholesterol, TG, VLDL, and LDL was found. In patients with albuminuria, LPLA was reduced compared to controls, however, the difference between the groups was not statistically significant [median (range)] 35.9 mU/g (20.4-103) versus 44.6 mU/g (28.2-57.2) and 40.9 mU/g (21.7-53.5) in group DA, C, and D0, respectively, p = 0.76. AER was not correlated to LPLA. An overall negative correlation between TG and LPLA was found; r = -0.33, p = 0.04, supported by an overall significant positive correlation between LPLA and HDL; r = 0.32, p = 0.045. We conclude that, in insulin-dependent diabetes mellitus, skeletal muscle lipoprotein-lipase activity is associated with plasma triglyceride, while an association between lipoprotein-lipase activity and urinary albumin excretion is questionable.