The efficiency of Spinosad was evaluated on larvae of the Egyption cotton leaf worm, Spodoptera littoralis (Boisd): (Lepidoptera: Noctuidae). Second instar larvae were more sensitive to Spinosad than 4^th instar larvae, as denoted by the determined LC₅₀ which was 5.73 and 7.83 ppm for 2^nd and 4^th instars, respectively. Meanwhile, LC₉₀ was 37.15 and 43.49 ppm for the respectively mentioned instars compared to their control. The duration of treated larvae was lengthened when either instars larvae were treated as compared to their control. Furthermore, percentage of pupation was reduced than the control by 51.03 and 49.5% when 2^nd and 4^th instar larvae were treated with LC₅₀ of Spinosad, respectively. Adult emergence was insignificantly affected as it was less than the control by 5.3 and 4.1% to the respective mentioned treated larval instars. The number of laid eggs was insignificantly affected; however, percentage hatchability was markedly reduced. The total protein content in larvae treated as 4^th instar showed a gradual increase from 2^nd and 6^th days after treatment as it was 34.79- 35.18 mg respectively, compared with 25.8 to 26.5 mg in control. The midgut tissue of 5^th instar larvae treated in the 4^th instar larvae with LC₅₀ of Spinosad showed some alternations and several aberration in some cell organelle such mitochondria, nucleolus,           microvilli and golgi apparatus as observed by light and electron microscope.