Substituted urea compounds are well-known as potent inhibitors of juvenile hormone epoxide hydrolase (JHEH) of the tobacco hornworm Manduca sexta. Docking simulations of 47 derivatives inside JHEH were performed to gain insight into the structural characteristics of these complexes. The obtained orientations show a strong similitude with the observed in the known X-ray crystal structures of human soluble epoxide hydrolase (sEH) complexed with dialkylurea inhibitors. In addition, the predicted inhibitor concentration (IC50) of the above-mentioned compounds as JHEH inhibitors were obtained by a quantitative structure-activity relationship (QSAR) method by using comparative molecular field analysis (CoMFA) applied to aligned dataset. The best models included steric and electrostatic fields and had adequate predictive abilities. In addition, these models were used to predict the activity of an external test set of compounds that was not used for building the model. Furthermore, plots of the CoMFA fields allowed conclusions to be drawn for the choice of suitable inhibitors.