The present study maybe is the first attempt in Egypt to evaluate the effect of Entomocidal proteins (Cry toxins) from Bacillus thuringiensis (Bt)Cry 1Ac and Cry 2Ab againstthe Egyptian cotton leafworm Spodoptera littoralis. The cotton leafworm one of the important Lepidopteran species is the most important pests in cotton fields. It can be controlled using Genetically Modified (GM) crops expressing insecticidal Bt proteins like Bt cotton and Bt corn. The long-term success of this technology demands pest resistance management. Important information for the successful management of resistance is the baseline susceptibility of the different target pests to the different Bt proteins. The data on baseline susceptibility should enable risk assessors and managers to assess whether GM cotton produces a Bt protein in a high-dose to specific target organisms and resistance has evolved during the commercial cultivation of this GM cotton event. During this study, the toxicity of Cry 1Ac and Cry 2Ab from the bacterium Bacillus thuringiensis to larvae of S. littoralis was assessed using first instar larvae with diet incorporation bioassays. Larvae reared (4 generations) from 2 populations of S. littoralis collected from major cotton-growing regions of Sohag and Assuit Governorates were tested. The LC₅₀ for the Assuit strain was 140.11 and 88.54 µg/ml forCry 1Ac and Cry 2Ab, respectively. While, the LC₅₀ for the Sohag strain was 410.75 and 37.62 µg/ml for Cry 1Ac and Cry 2Ab, respectively. On the other hand, the laboratory strain was more sensitive for the same Cry's (Cry 1Ac and Cry 2Ab) the LC₅₀ was13.40 and 0.23 µg/ml, respectively. The lethal concentration (LC₅₀) against S. littoralis for 2^nd and 4^th instars larvae when using the B. thuringiensis as spores (commercial product) was 1.16 and 2.49 for 2^nd and 4^th instars, respectively. This study is very important as a preliminary step and baseline ahead of the commercial cultivation and production of Genetically Modified cotton (Bt cotton).