Nephrotic Syndrome (NS) is associated with elevated plasma concentration and impaired clearance of VLDL, chylomicrons (CM) and their atherogenic remnants. These abnormalities are largely due to lipoprotein lipase, hepatic triglyceride lipase and VLDL receptor deficiencies and impaired HDL-mediated shuttling of ApoE and ApoC between the nascent and the remnant VLDL and CM. LRP is a multifaceted endocytic receptor which is heavily expressed in the liver. LRP recognizes at least 30 different ligands including VLDL and CM remnants. These observations prompted the present study to discern the effect of NS on hepatic LRP gene and protein expressions. The study further sought to explore the effect of lipid-lowering therapy on LRP expression in NS. Sprague Dawley rats were randomized to the NS (given IP injections of puromycin aminonucleoside 130 mg/Kg on day 1 and 60 mg/Kg on day 14) and placebo-injected control groups. On day 14, the animals were subdivided into the statin-treated (rosuvastatin 20 mg/Kg/day mixed with powdered chow) and untreated groups and studied on day 28. The untreated NS group exhibited severe proteinuria, hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia and marked elevation of hepatic tissue LRP mRNA and protein abundance. Statin administration for two weeks resulted in significant improvements of plasma lipid profile, proteinuria, hypoalbuminemia, as well as, hepatic LRP mRNA and protein abundance. In contrast, statin administration had no significant effect on either plasma lipids or hepatic LRP levels in the normal control rats. In conclusion, nephrotic syndrome results in marked upregulation of hepatic LRP expression which is partly reversed with statin administration. These findings exclude depressed hepatic LRP expression as the primary cause of the elevated plasma lipoprotein remnants in NS.