In this study a lipotropic chitosan derivative, O-oleoyl-chitosan (OOCs), was obtained through the attachment of oleoyl groups to hydroxyl groups at C-6 of chitosan. The degree of substitution of OOCs was approx. 14-15%. OOCs had good solubility in organic solvents. Lipoprotein sorption tests in vitro and circular dichroism spectroscopy were applied to investigate the interaction between lipoproteins and OOCs. Observations indicated that the lipotropic OOCs, especially with lower viscosity-average molecular weight, could improve both LDL binding capacity and selectivity in human plasma. Circular dichroism analysis showed that the secondary structure of LDL was markedly changed by OOCs, for the α-helical content of the LDL was increased when interacted with OOCs. OOCs were proven to be effective for selective removal of LDL in plasma.