Protease cascade in insect hemolymph is important in proper response against invading microorganisms and parasitoids. Serine proteases lead to the induction of antimicrobial peptide syntheses and phenoloxidases. In the current study, the effects of the least concentration of the three specific inhibitors of serine proteases including AEBSF.HCl [4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride], TLCK [tosyllysine chloromethyl ketone hydrochloride] and TPCK [tosyl phenylalanyl chloromethyl ketone] were evaluated on the activities of trypsin, chymotrypsin, elastase and phenoloxidase of Cydalima perspectalis larvae. The 5 µM concentration of AEBSF.HCl lead to the significant decrease of trypsin, chymotrypsin and phenoloxidase activities at the time intervals of 1, 15, 30- and 60-min post-injection while the activities reached to the value of control after 120 and 180 min. The inhibitor showed no significant effect on elastase activity. The 5 µM concentration of TLCK also decreased the activity of trypsin at the time intervals of 1, 15, 30- and 60-min while the activity of phenoloxidase decreased at all-time intervals except for 180 min post-injection which the least value was obtain after 15 min of injection. TPCK decreased the activity of chymotrypsin at all-time intervals following injection except for 180 min in which the least activity was recorded after 1 min. This inhibitor decreased the activity of phenoloxidase at the time intervals of 1, 15 and 30 min after injection while no significant differences were observed at other time intervals. These results demonstrate the important role of serine proteases in induction of phenoloxidase within C.perspectalis larvae. Inhibitors used in this study can prevent effective immunity of insects by stopping the serine protease process in insect hemolymph and increase the sensitivity of larvae against pathogen. In other words, the use of these compounds improves the effective control of pests through microbial control.