The widespread use of the insecticides for controlling the destructive pest, red palm weevil (Rhynchophorus ferrugineus), raises the question about efficacy the chitin synthesis inhibitors (CSIs). Therefore, this study aims to explore the tested CSIs acute toxicity on the field strain of red palm weevil. Also, some biochemical changed in the 6th instar larvae after treatment with tested LC50s were measured. The LC50 values of chlorfluazuron, hexaflumuron, and lufenuron were determined at 454.01,1293.02 and 919.13 µg/ml, respectively for the 6th larval instar exposed using the food dipping method. The lufenuron showed the lowest significant reduction in total protein (7.29%) accompanied with activation GST, ß-esterase, carboxylesterase, phenoloxidase, chitinase, and ɑ- Esterase recorded 58.50, 58.54, 26.09, 22.56, 11.52 and 7.77% increasing respectively. The chlorfluazuron showed mediated significant reduction in total protein (23.54%) accompanied with activation GST, ß-esterase and carboxylesterase and chitinase recorded 24.90, 23.94, 4.89 and 2.28 % increasing respectively. The highest significant reduction in total protein (45.96%) with hexaflumuron treatment accompanied with activation GST, carboxylesterase and chitinase recorded 48.02, 38.86 and 25.22% increase respectively