The objective of the present investigation was to explore the potential of the Chitosan Oligosaccharides (COS)-coated NLC (nanostructured lipid carrier) for ocular drug delivery. NLC loaded with flurbiprofen was prepared by melt-ultrasonic method and then coated with COS with a molecular weight of 3000-6000kDa. After coating, the particles reflected spherical morphology with smooth surface under transmission electron microscope (TEM) analysis and a changed zeta potential from -0.446mV to +20.7mV. The ocular bioadhesion property was evaluated by Gamma scintigraphic technique, revealing that the clearance of the formulations labeled with radioactive 99(m)Tc-DTPA was significantly delayed in the presence of COS, and the AUC of the COS-coated formulation had a 7.7-fold increase comparing with non-coated ones. Additionally, enhanced transcorneal penetration was achieved by using the COS coating with a corresponding apparent permeability coefficients (P(app)) which had a 2.4-fold increase comparing with the reference. Consequently, COS coating modified the properties of NLCs and presented a series of notable advantages in ophthalmic application.