The susceptibility to IGRs, moulting hormone agonist, mimic (tebufenozide) and chitin synthesis inhibitors match (lufenuron) was studied in the 2nd and 4th larval instars of the cotton leafworm Spodoptera littoralis (Bosid). Obtained results revealed that match was the more toxic against 2nd larval instars at sub- lethal concentrations LC25 and LC50 (0.3 and 0.6 ppm, respectively) than mimic (1.1 and 1.5ppm, respectively). But LC90 level was the same in the two IGRs. With respect to 4th larval instar, match induced the higher toxic effect at all sub lethal doses than mimic. Biochemical analysis showed that match and mimic exhibited a severe reduction in the activities of the detoxification enzymes, acid phosphatase and esterases (α and β), as compared to the control. The enzymatic activities were inhibited with the increase in the time posttreatment and also with the increase in dose. Therefore, the tested IGRs, tebufenozide and lufenuron , may be not detoxify by these enzymes.