Abstract: To improve water solubility of diethyltoluamide (DEET), DEET/β-cyclodextrin (DEET/β-CD) inclusion compound was prepared by homogeneous coprecipition method. Differential scanning calorimetry (DSC) and XRD were used for the characterization of the inclusion compound. Then DEET/β-CD/O-CMC nanocapsules were prepared via a cross-linking reaction. DEET/β-CD/O-CMC nanocapsules were determined by UV spectrophotometer, mastersizer and SEM. Finally, the drug release property of DEET/β-CD and DEET/β-CD/O-CMC was studied. An inclusion complex was formed in 1:1 molar ratio. DEET solubility in the water was improved 27 times by introducing β-CD into the system. And the encapsulation efficiency and loading capacity of the prepared nanocapsules were (79.93±2.08) % and (12.11±0.09) %, respectively. The nanocapsules were oval in shape with average particle sizes of (230.50±11.34) nm, Zeta potential of (–19.08±0.99) mV, and PDI of 0.055. Release studies in Tris-HCl (pH = 7.4) evidenced β-CD/O-CMC nanocapsules have better sustained-release effect than DEET/β-CD. The DEET in DEET/β-CD/O-CMC and DEET/β-CD was released 27.04% and 38.10% within 24 h, respectively.