Antimicrobial immune response is mediated by a signal-transducing sensor, peptidoglycan recognition protein-SA (PGRP-SA), that can recognize non-self molecules. Although several studies have focused on the involvement of PGRP-SA in antimicrobial peptide (AMP) expression in response to infections, studies on its role in are lacking. Here, we present a functional analysis of PGRP-SA (PGRP-SA). In the absence of microbes, was highly expressed in the late-larval fat body, followed by hemocytes, and gut. Interestingly, following , , and infections, the mRNA level of was significantly upregulated in both the fat body and gut. silencing had a significant effect on the mortality rates for all the microbes tested. Moreover, is required for regulating the expression of eight AMP genes namely , -, and ; and ; ; and and in the fat body in response to and infections. is essential for the transcription of , ; ; , ; and , , and in the gut upon and infections. However, does not regulate AMP expression in the hemocytes. Additionally, Dorsal isoform X2, a downstream Toll transcription factor, was downregulated in -silenced larval fat body following and challenges, and in the gut following and challenges.