Biopesticides are biologically-derived agents, that are usually applied in a manner similar to chemical pesticides, but achieve pest management in an environmentally-friendly way. Among the most promising biopesticides, is the bacterial insecticide; Spinosad and Emamectin benzoate. Therefore, in the present study, fourth instar larvae of S. littoralis were allowed to feed on leaves previously dipped with 1, 10, 50 and 100 ppm of spinosad and 0.5, 1, 2 and 10 ppm of emamectin benzoate for 72 hrs and then were used to screen alterations in protein profiles and DNA by using SDS- PAGE and RAPD-PCR, respectively. Results of SDS-PAGE analysis revealed that the protein profiles of S. littoralis changed after larval treatment with spinosad and emamectin benzoate and new proteins were observed in treated larvae. RAPD technique was used to detect genetic differences between control and fourth instar larvae of S. littoralis which treated with spinosad and emamectin benzoate.