plant proteinase inhibitors were (PIs) extracted from tomato leaves (Solanum lycopersicum L.) to test their effect on the digestive physiology of Spodoptera littoralis in relation to growth and development of the larvae. Larvae fed on leaves treated by crude extract protein of PIs (10 mg protein m1-1). The continuous feeding of the cotton leafworm on treated leaves from egg hatching led to significant inhibition of the 4th larval instar gut proteases (decreased by 32.9% as compared to control). Effects of PIs on protein digestion suggested that PIs might alter protein metabolism. The results showed that total proteins were significantly reduced in treated larvae as compared to control (P< 0.05), but free amino acids were more affected than proteins (P< 0.01). Also, enzymes related to protein metabolism were also changed due to feeding on leaves treated by PIs. On the other hand, the study revealed that continuous feeding on tomato PIs reduced S. littoralis larval and papal weight, and caused 6.7% abnormalities i.e. appearance of larval-pupal intermediates. It could be suggested that tomato PIs act by in vivo inhibiting of the cotton leafworm gut proteases, not by resulting in hyperproduction of proteolytic enzymes related to protein metabolism such as Glutamic oxaloacetic transaminase (GOT) to compensate the reduced amount of available proteins due to treatment. It is the first time to test PIs activity towards the native pests. Results presented here demonstrating that the use of tomato PIs might be of a significant value in the field of pest control.