Abstract: The microstructures of ibuprofen-hydroxypropyl-β-cyclodextrin (IBU-HP-β-CyD) and ibuprofen-β-cyclodextrin (IBU-β-CyD) were observed by atomic force microscope (AFM). The high resolving capability of AFM has the tungsten filament probe with the spring constant of 0.06 N·m^-1. Samples were observed in a small scale scanning area of 10.5 nm×10.5 nm and 800×800 pixels. The original scanning images were gained by tapping mode at room temperature. Their three-dimensional reconstruction of microstructure was performed by G3DR software. The outer diameters of HP-β-CyD and β-CyD are 1.53 nm. The benzene diameter of IBU is 0.62 nm, fitting to the inner diameters of HP-β-CyD and β-CyD. The benzene and hydrophobic chain of IBU enter into the hole of cyclodextrin at 1∶1 ratio. The results were evidenced by IR, X-ray diffraction and the phase solubility.