To investigate the possibility of engineering a glycocalyx-like surface via end-tethered hydrophobic ligand onto poly(ethylene oxide) (PEO), polystyrene-graft-[omega-stearyl-poly(ethylene oxide)] (PS-g-SPEO), which has poly(styrene) backbone and PEO side chains end-functionalized with stearyl groups, was specifically prepared. X-ray photoelectron spectroscopy results indicated that SPEO was enriched at the surface. Differential scanning calorimetry results revealed that the stearyl end groups tended to assemble a stable stearyl phase, which could be destroyed by a thermal treatment. A "looplike" SPEO (sample A) and a "tail-like" SPEO (sample B), which had almost the same surface composition, were then used as model surfaces to study the surface architecture of end-tethered PEO in aqueous environment. The contact angle at the sample A/water interface decreases rapidly with increasing of the water hydration time. After longer water incubation, it presented a hydrophilic interface with the low PEO mobility. Sample A was shown to impart significant resistance to both albumin and fibrinogen adsorption. But it is nonselective for the albumin. By contrast, the contact angle at the sample B/water interface decreases little with water hydration. It presented a hydrophobic interface with the high ethylene oxide mobility. Sample B exhibits a very low fibrinogen adsorption while adsorbing a high level of albumin. All above results proved that sample B may keep a "tail-like" SPEO in aqueous solution and it is possible to get a glycocalyx-mimic surface, in which a hydrophobic matrix was covered by a layer of flexible hydrophilic PEO and then by hydrophobic signal molecules.