Objective Accumulation of amyloid β (Aβ) in the brain is known to be involved in the pathogenesis of Alzheimer's disease (AD). Low-density lipoprotein receptor-related protein 1 (LRP1) in brain mivrovascular endothelial cells is known to be a transporter that export Aβ across the blood-brain barrier (BBB). In this study, the effect of rosiglitazone, a peroxisome proliferatoractivated receptor-γ (PPARγ) agonist on the expression and function of LRP1 was investigated in primary human brain microvascular endothelial cells (HBMECs). Methods HBMECs were treated with various concentration of rosiglitazone for 48 h. The expression of LRP1 in HBMECs was investigated through immunobloting and RT-PCR. Luciferase assay using the LRP1 promoter-reporter vector was performed. The cellular uptake of Aβ40 and Aβ42 was also evaluated. Results Rosiglitazone up-regulated the amount of LRP1 mRNA and the protein expression in HBMECs in a dose-dependent manner in up to 10 nM of rosiglitazone concentration. Luciferase assay showed that rosiglitazone activated the transcription of the LRP1 promoter by PPARγ. Aβ40 and Aβ42 uptake through LRP1 in HBMECs also increased by rosiglitazone. This increase of the LRP1 promoter activity and Aβ uptake was observed in up to 10 nM of rosiglitazone concentration. At concentrations above 20 nM of rosiglitazone, the LRP1 expression, the LRP1 promoter activity, and Aβ uptake in HBMECs were not altered compared to those in non-treated cells. The effective range of rosiglitazone concentration on LRP1 expression and function in HBMECs was much lower than that in adipocytes or hepatocytes. Conclusion In conclusion, this study suggests a new therapeutic application of rosiglitazone for AD at much lower dose than the average doses used for T2DM treatment. This "low-dose rogiglitazone treatment" is expected to reverse the key pathogenesis of AD through enhancing clearance of Aβ in the brain.