Abstract: To study the resistance mechanism of Spodoptera frugiperda (FAW) to diamide insecticides, the three-dimensional structure of the transmembrane region of FAWRyR was constructed by homologous modeling based on its amino acid sequence in this work. It was found those two had high homology degree compared with the amino acid sequence of FAW and Plutella xylostella (DBM) RyR. In addition, the mutation was introduced into the model of FAWRyR according to the reported mutation site of FAWRyR (I4734M) and DBMRyR mutation site G4946E (corresponding to G4891 in FAWRyR), and the binding modes between the wild-type (WT) & mutant FAWRyRs and five kinds of diamides were analyzed by molecular docking. The binding affinity between the substitutions I4734M and diamides showed no significant difference, compared with that between WT FAWRyR and diamides. Both the substitution I4734M and WT FAWRyR existed important non-covalent interactions, such as hydrogen bond, halogen bond, hydrophobic interaction, π-stacking and π-cation interaction. However, the substitution G4891E produced reduction in binding affinity and the number of action mode, which affected the binding stability of FAWRyR and diamides. These results indicated that the substitution G4891E could cause the resistance of FAWRyR to diamides. And future research should focus on the G4891E mutation of FAWRyR. Moreover, this reserch could provide a reference for RyR-structure-based insecticides design.