The toxicity of chlorantraniliprole (an anthranilic diamide) and lufenuron (an insect growth inhibitor) against the 2^nd and 4^th instar larvae of the cotton leafworm, Spodoptera littoralis (Boisd.) was investigated. The in vivo effects of chlorantraniliprole and lufenuron on the activity of each of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatases (ALP) activities of the S. littoralis 4^th larval instar were also assessed. The bioassay of the 2^nd instar larvae revealed that chlorantraniliprole (LC₅₀ = 0.009, 0.005 and 0.003 mg/l) was approximately as 234.3, 206.2 and 226.3 fold more toxic than lufenuron (LC₅₀ = 2.019, 1.031 and 0.679 mg/l) after three different exposure periods (48, 72 and 96 hrs, respectively).  Concerning the 4^th instar larvae, chlorantraniliprole (LC₅₀ = 6.645, 0.028 and 0.006 mg/l) was approximately as 2.01, 105.36 and 226.3 fold more toxic than lufenuron (LC₅₀ = 13.37, 2.95 and 1.87 mg/l) after 48, 72 and 96 hrs of exposure, respectively. In vivo effect of chlorantraniliprole and lufenuron enhanced the activity of AST and ALT and that enhancement was concentration and time of exposure dependent. Both chlorantraniliprole and lufenuron inhibited ALP activity; which was also concentration and time of exposure dependent. Based on the obtained results, chlorantraniliprole and lufenuron would be involved within the current foliar insecticide applications used for controlling S. littoralis in cotton fields.