The study mainly aimed at the effectiveness of bee venom which is a natural product and overcame antibiotic resistance and side effects on the second instar of cotton leaf worm Spodoptera littoralis (lepidoptera: Noctuidea) that is one of the most common insect pests. Four different doses of bee venom were treated (0.125gm,0.25gm, 0.5gm and 1gm) to evaluate total morality of second and forth instars larvae of S. littoralis. The results showed that 16.67%, 30%, 53.33%, 76.66% were total morality percentage, respectively. In addition, the 4th instar larvae of S. littoralis were treated by LC50 to study the histological changes in the mid gut after 3 and 5 days. The changes were completely separation or destruction of basement membrane and sever proliferation of epithelial cells after the two days, but the midgut in control was identical.