The development of indigenously isolated entomopathogenic nematodes as biological control agents was investigated. The study involved two nematode species (Steinernema riobrave and Heterorhabditis bacteriophora Poinar (HP88 strain) and their pathogenicity against larvae of pink bollworm, Pectinophora gossypiella, under laboratory conditions. The observed mortality caused by the both tested nematodes at different time intervals was recorded. The establishment of nematodes in a host depends greatly on its ability to manage host defenses so, total larval body contents (total protein and free fatty acids) were recorded as well as activities of detoxification enzymes (peroxidase and phenoloxidase) were screened. Results indicated that, the two nematodes had variable significantly effects. S. riobrave recorded a highly significantly affect than H. bacteriophora. In addition, there are relationship between mortality rate and time exposure of both nematodes against P. gossypiella larvae, the susceptibility increased with the time exposure increased. Total proteins content significantly increased after treatment with S. riobrave (24.58 mg protein/gbwt).Whilst H. bacteriophora caused a non-significant increase in the proteins content (22.95 mg protein/gbwt). In addition, it is could be noted that, female showed a slight significant increase in total proteins content (23.81 mg protein/gbwt) than male (23.10 mg protein/gbwt). Both nematode species increased the free fatty acids than control and the contents of free fatty acids were higher in female (1355.78 ug triolein/gbwt) than male (469.33 ug triolein/gbwt). Nematodes, H. bacteriophora and S. riobrave showed the lowest enzyme activities of phenoloxidase (17.87 and 17.72 OD units/min/gbwt, respectively). In addition, values recorded for male and female did not differed significantly. Data demonstrated that peroxidase activity of the pink bollworm larvae was higher in female than male. The enzyme activity increased relative to control by 13.55 and 74.92% in the case of H. bacteriophora male and female with values of 3.10 and 5.79 Δ OD 430/min/gbwt, respectively. In conclusion, we can say that the all parameters determined were higher in female than male, except in the case of phenoloxidase. Entomopathogenic nematodes, S. riobrave and H. bacteriophora can play an important role in defeating the host immune system and can control larvae of P. gossypiella.