The present investigation aimed to throw light on the efficiency of two novel insecticides, pyridalyl and emamectin benzoate(contact), a semi-synthetic insecticide on two different larval instars (2^nd and 4^th) of the cotton leafworm, Spodoptera littoralis (Lepidaptera: Noctuidae). Also to study their toxic affects on some biochemical parameters on albino rat. The results clearly showed that pyridalyl was more toxic than emamectin benzoate against the 2^nd and 4^th larval instar according to LC₅₀ values after all time post exposure (2, 3, 5 and 7 days). In addition the two tested compound decreased pupal weight, pupation and adult emergence percentages resulted from larvae treated with different concentrations of these insecticides as 2^nd and 4^th larval instars. The present study also animals were treated orally with (1/10 LD₅₀) of each compound done by using sixty male adult albino rats were divided into three groups .First group "control" was received distilled water daily, second group were received repeated oral administration of 0.07mg/animal/day of pyridalyl and third group were received repeated oral administration of 2.5 mg/animal / day of emamectin benzante for 28 consecutive days. The results showed that there were significant increases of ALT, AST, urea and creatinine in the treatment of Pyridalyl more than emamectin benzante and control. On the other hand there were significant decreases in protein content in the treatment of Pyridalyl more than E. benzante on comparison with control. Conclusion: The results indicated the toxic nature of the insecticide pyridalyl is more than E. benzante on Spodoptera littoralis and albino rats so we suggest that usage of E. benzante although it less toxic to save environment