The present study was carried out to investigate the efficancy of substerilizing doses of gamma irradiation or/ and entomopathogenic fungi Beauveria bassiana and Metarhizium anisopliae on the humoral immune enzyme response of Spodoptera littolaris larvae. It was found that gamma irradiation of male pupae (50,100&150 Gy) decreases the humoral immune enzyme activity (phenoloxidase, prophenoloxidase, lysozyme) and protein concentration compared to the control of the 6^th instar larvae S. littolaris. Injecting of  Lc₅₀ concentration of both B. bassiana (0.4x10⁵sp/µl)  and M. anisopliae (8x10⁸sp/µl) to the last 5^th instar larvae of S. littolaris were significantly increased phenoloxidase, prophenoloxidase, lysozym activities  and protein concentration after one day, however, they were significantly declined on the second, third and fourth days and remained at a level lower than that of the controls. Both gamma irradiation and entomopathogenic fungi (B. bassiana and M.anisopliae) significantly decreased the immune enzyme activity and protein concentration (p≤ 0.05) after 2, 3 & 4 days. However, this decrease was remarkable in the larvae of irradiated males'pupae (100Gy) which were injected with entomopathogenic fungi. In conclusion, gamma radiation and tested entomopathogenic fungi synergistically inhibitthe immune system of Spodopteralittolaris larvae.