Abstract: In this study, a novel core-shell structured nanocarriers for oral delivery of insulin were developed. Firstly, chitosan nanoparticles (CS-NP) was prepared by cross-linking of chitosan with triphosphate TPP as the core of the core-shell structured nanocarriers. Then lipid coating chitosan nanoparticles (LCS) and pluronic F127 modified lipid coating chitosan nanoparticles (FLCS) were prepared by co-incubation of CS-NP with EPC liposomes or pluronic F127 modified EPC liposomes, respectively. The morphologies of the nanocarriers were observed using transmission electron microscope (TEM). These nanocarriers were also characterized in terms of the stability of insulin in the nanocarriers, mucus penetrating properties, and cellular association efficiencies. Under TEM a core-shell structure could be observed in FLCS indicating CS-NP formed the core which was coated with lipids. FLCS had an average diameter of 195 nm with a zeta potential of -4.3 mV. In vitro degradation study showed that with the phospholipids layer, FLCS could protect the chitosan associated insulin from degradation by trysin and α-chymotrpsin. Cellular association study performed on Caco-2 revealed that the cell association of FLCS was around 2 folds higher than CS-NP and LCS. Compared to CS-NP and LCS, FLCS exhibited enhanced mucus penetration properties in in vitro mucus penetration study. In summay, the coronal core-shell structured nanocarriers presents a promising particles for effective oral insulin delivery by combing the effects of enhancing the stability of inulin in GI tract, improving mucus penetration perperty and facilitating cellular association.