Abstract: The three-dimensional models of the transmembrane domain of zebrafish (Danio rerio) GABAA receptor and fruitfly (Drosophila melanogaster) RDL receptor were constructed by homology modeling based on the pore structure of nicotinic acetylcholine receptor, and the differences of fipronil binding sites in the two receptors were discussed. Molecular docking and molecular dynamics were used to investigate the different interactions between fipronil and the two receptors. The results indicated that the sequence identity was high, but the structure of fioronil binding sites in the two receptors were different. In zebrafish GABAA receptor, fipronil located at the bottom of the transmembrane domain, while in fruitfly RDL receptor, fipronil located within the region from Ala301 to Leu308. The two receptor-fipronil complexes were stable after molecular dynamics simulation. There were 4 hydrogen bonds generated between fipronil and zebrafish GABAA receptor, two of them whose frequency were higher than 60%. While, there were 6 hydrogen bonds in fruitfly RDL receptor-fipronil complex, but only one hydrogen bond with frequency higher than 50%. It was clear that the stability of fruitfly RDL receptor-fipronil complex was lower than that of zebrafish GABAA receptor-fipronil complex.