Cypermethrin, esfenvalerate, chlorpyrifos and Bacillus thuringiensis, Kurs. were tested against the cotton leaf worm, Spodoptera littoralis (Boisd.) treated as 4^th instar larvae. In addition, LC₅₀ ^,s of tested compounds were applied on S. littoralis larvae to investigate the ultra structural changes in the integument, muscle, fat body and mid gut of alive and dead larvae. Meanwhile, the nerve cord sections were investigated for alive larvae only. All investigations were done by light and electronic microscopes. Cypermethrin was the most potent compounds against S. littoralis larvae, followed by esfenvalerate, chlorpyrifos and then B. thuringiensis that had the least toxicity on the cotton leaf worm compared to other tested compounds. Ultra structural investigations showed that cypermethrin caused thickening of outer cuticle fibrous layer in the integument of S. littoralis larvae. Also, hypodermis layer had swelling at the same treatment and necrosis in other treatments. In addition, all the treatments caused appearance of fissure and breaking down of muscles into small parts. While, all tested compounds except B. thuringiensis caused swelling in the integuments of dead larvae compared to control. On the other hand, B. thuringiensis caused drastically necrosis in the integument and hypodermis layers of dead larvae. All the compounds caused a noticeable destruction on the fat body cells as well as vacuolization and destruction the fat body membranous sheath.Many deleterious effects in the mid gut of S. littoralis as destruction of columnar or hyperphesia cells lining mid gut, losses of brush border with increase of goblet cells. Mid gut of died larvae had the highly destruction as affected by cypermethrin treatment. Meanwhile, other treatments caused shrinking in mid gut parts and necrosis in another parts. Neurosecretory cells of S. littoralis larval nerve cord had shrunk and dwarfed in cypermethrin, chlorpyrifos and B. thuringiensis, while; it had swelling in esfenvalerate treatment. Also, nucleus and nerve cells were disappeared partly in the most treatment compared to control.