BACKGROUND The pathophysiologic mechanisms behind the development of liver steatosis during total parenteral nutrition (TPN) and the possible relationship to alterations of lipoprotein lipase activities in different tissues are not fully known. It is also unknown whether continuous and discontinuous administration of TPN affect lipid metabolism differently. METHODS TPN, including 8.4 g of triglycerides per kilogram per day, was given for 10 days to two groups of male Sprague-Dawley rats that received the infusions discontinuously and continuously, respectively. Freely fed rats were used as controls. RESULTS TPN led to hyperlipidemia and accumulation of triglycerides in the liver. High-density lipoproteins were enriched in triglycerides, whereas high-density lipoprotein cholesterol and phospholipid levels were low. The activities of hepatic lipase were markedly decreased, and lipoprotein lipase activities in adipose tissue and in cardiac muscle were both up-regulated. The increased levels of cholesterol and phospholipids in the serum of TPN animals were more pronounced after discontinuous administration. CONCLUSIONS TPN including lipids interferes with the normal regulation of lipid metabolism. Although the mechanisms remain obscure, the elevation of lipoprotein lipase activities seems functionally important to accommodate the increased input of triglycerides during TPN. Possibly, the observed alterations in lipase activities may be attributed to a state of hypothyroidism.