Background. Postprandial lipoproteins enhance inflammatory activity, but the mechanisms of this action remain unclear. Objectives. The aim of the study was to determine postprandial lipemia in hyperlipemic subjects and to study the relationship between lipids and high-sensitivity C-reactive protein (hs-CRP) in fasted and postprandial states. Material and Methods. Blood samples were taken from 148 men (60 normolipemic, 27 hypertriglyceridemic, 49 hypercholesterolemic, and 12 with mixed hyperlipemia) in a fasted state and three hours after a standardized high-fat meal (1500 kcal) three times: before and after 6 and and 12-weeks of therapy with simvastatin (20 mg//day) and/or fenofibrate (267 mg/day). Triglycerides (TG), total lipoprotein, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and HDL2-and HDL3-cholesterol were measured by routine methods, apolipoproteins A and B by immunoturbidimetry, and hs-CRP by immunonephelometry. Results. At the start of the study the mean hs-CRP level was increased (p < 0.05) in the hyperlipemic vs. the normolipemic men whereas the mean postprandial triglyceride increase (Delta TG) was higher (p < 0.05) in the men with hypertriglyceridemia. However, fasting TG (TG(o)) > 400 mg/dl was associated with low. TG and TG(o) < 400 mg/dl with high TG changes. Hypolipemic therapy caused a reduction in postprandial TG changes in all the hyperlipemic men. Linear correlation between the concentrations of TG and HDL as well as HDL3-cholesterol was found. Positive correlation between TG(o) and hs-CRP concentrations coexisted with a negative relationship between HDL3-cholesterol and hs-CRP only in the control group. Statin restored the relationship between the concentrations of HDL3-C and hs-CRP in the hypercholesterolemic men. Conclusions. Increased postprandial lipemia in hyperlipemic men was associated with increased inflammatory activity and HDL3-cholesterol seems to have anti-inflammatory properties. Hypolipemic therapy decreased postprandial lipemia and at least partially recovered regulatory function in lipid homeostasis (Adv Clin Exp Med 2010, 19, 1, 89-98).