The growth and development of Spodoptera littoralis (Lepidoptera: Noctuidae) larvae strongly inhibited by Hyptis brevipes (Lamiaceae) dichloromethane extract. The present study evaluates the antifeedant activity of dichloromethane extract of H. brevipes against the 5th larval instar of S. littoralis using castor bean leaf disks. The results from the no-choice bioassay showed that this extract caused antifeeding effect by 58.3% ± 6.3and 76.7±5.5 % at concentrations of 2% and 4%, respectively. The histological changes in the midgut and Malpighian tubules of S. littoralis larvae elicited by H. brevipes dichloromethane extract were also evaluated. Two concentrations (2% and 4%) of this extract were orally applied to the 3rd instar larvae of S. littoralis for three consecutive days. The extract induced many histological changes in the tested organs in a time and dose dependent manner. At a concentration of 4% of H. brevipes extract, the peritrophic membrane was detached and the mid gut lumen was packed with pycknotic-nuclei-epithelial cells. Extensive destruction of the epithelium with cells lacking nuclei was also observed in the mid gut of larvae treated with 2% after 7 days of treatment. Architecture destruction of the Malpighian tubules of S. littoralis larvae treated with 4% of H. brevipes extract was observed 4 days of treatment. Histochemically, the total protein content was decreased in the mid gut cells of the treated larvae compared to control. The target organ for this toxic material is the mid gut and Malpighian tubules as indicated by their high sensitivity toward H. brevipes extract. This sensitivity could be in part responsible for the antfeeding activity of this plant extract and the deleterious effect on larval mortality and thus enhance the possibility of using this plant extract in the control program of S. littoralis.