To identify the nuclear receptors (NR) mediate CYP450 induction in insects, we employed the fat body cell line of Lymantria dispar (IPLB-LdFB) as a model system. Cypermethrin was treated to the IPLB-LdFB, and the level of CYP450 induction was determined by ethoxyresorufin-O-deethylase (EROD) assay. CYP450 activity increased according to the induction time (ca. two-fold after 9-hr induction) in the cypermethrin-treated IPLB-LdFB compared to non-treated ones. CYP450 activity was also increased by the pretreatments of carbaryl and 3-methylcholanthrene, but not by monocrotophos. To search for NR that mediate the cypermethrin-induced CYP450 expression, comparative 2-dimentional electrophoresis was conducted using soluble proteins from both cytosol and nuclear fractions of the IPLB-LdFB with or without cypermethrin pretreatment. One spot that was more expressed (or localized) in the cypermethrin-treated cells, particularly in nuclear, was determined by tandem-mass analysis to be similar to the steroid and xenobiotic receptor (SXR) that is known to regulate CYP450 activity in mammals. By homology probing, we amplified and cloned the full-length cDNA fragment of SXR-like gene that possesses both ligand- and DNA-binding domains from the IPLB-LdFB. Preliminary RNAi using a 720-bp dsRNA was employed to silence the SXR-like NR in IPLB-LdFB, and real-time PCR was conducted to determine the reduction level of its transcript. The RNAi resulted in ca. 22% reduction in the level of the SXR-like gene transcript and ca. 30% suppression of the CYP450 induction by cypermethrin treatment compared to control cells. These findings suggested that the SXR-like NR in IPLB-LdFB appears to mediate CYP450 induction by cypermethrin.