The objective of this research was to evaluate the toxicity of new type of insecticides mixtures (insecticide + insecticide + synergist) to 4^th instar larvae of cotton leafworm spodoptera littoralis in addition to study the effect of this mixtures and their individual insecticides on some biochemical enzymes activites in hemolymph in 4^th instar larvae. Toxicological Results revealed that cordon plus was the most effective insecticides mixture with LC₅₀ (11.04 ppm) followed by lambada 5%, encore and pulmic. While chlorpyrifos was the most effective individual insecticide against 4^th instar larvae of cotton leafworm S. littoralis with LC₅₀ (46.17 ppm) followed by fenitrothion, diazinon and lambada 2.5%. Biochemical results revealed that all the tested insecticides increased the activity of aliphatic esterase except chlorpyrifos and there was appositive correlation between the concentration used and the activities. All the tested insecticides decreased (α-E), all the tested insecticides increased (ß -E) .Also all the tested insecticides and insecticides mixtures increased acid phosphatases and alkaline phosphates activities when larvae treated with LC_12.5 or LC₂₅, in comparison with control. All the tested compound decreased (GOT /AST) and (GPT /ALT)activites in hemolymph of 4^th instar larvae of S. littoralis