The properties of mucus in a person with asthma can alter with disease process so that it may lead to the airway embolism. Fe2O3 nanoparticles can be used for drug delivery. Up till now, however, little is known about how the Fe2O3 nanoparticles influence the properties of airway mucus. In this study, Fe2O3 nanoparticles were dispersed with ultrasound, and the morphological properties were measured with scanning electron microscope, atomic force microscope and nanometer laser particle size and zeta potential analyzer. Then the dispersed Fe2O3 nanoparticles were added to the simulated asthma airway mucus with different final concentration (0.03, 0.3, and 0.4 mg/mL). The measurements of flow curve, yield stress, large amplitude oscillatory shear (LAOS) and shock scanning were carried out with a rotational rheometer. Experimental results showed that the Fe2O3 nanoparticles reduced the zero shear viscosity of simulated asthma airway mucus. With increase of shear rate, the wind speed of mucus was reduced. The yield stress of simulated asthma airway mucus was 19.0 Pa, but the yield stresses of experimental group (0.03, 0.3 and 0.4 mg/mL) were 17.0, 0.99, and 0.7 Pa, respectively. The results showed that the viscoelastic modulus of asthma airway mucus treated with Fe2O3 nanoparticles were changed obviously as measured with large amplitude scanning and frequency scanning. By adopting the method of optical phase microscopy, we found that different structures of simulated airway mucus were absorbed. The results showed Fe2O3 nanoparticles distroyed mucus structure. The experimental results proved that Fe2O3 nanoparticles could change the rheological characteristics of simulated asthma airway mucus. This experimental result would lay a foundation for the further development of airway mucus sticky agent based on the function of Fe2O3 nanoparticles.