Lipid droplets (LDs) are dynamic organelles that participate in the regulation of lipid metabolism and cellular homeostasis inside of cells. LD-associated proteins, also known as perilipins (PLINs), are a family of proteins found on the surface of LDs that regulate lipid metabolism, immunity, and other functions. In silkworms, pébrine disease caused by infection by the microsporidian () is a severe threat to the sericultural industry. Although we found that relies on lipids from silkworms to facilitate its proliferation, the relationship between PLINs and proliferation remains unknown. Here, we found infection caused the accumulation of LDs in the fat bodies of silkworm larvae. The characterized perilipin1 gene () promotes the accumulation of intracellular LDs and is involved in proliferation. is similar to in humans and is conserved in all insects. The expression of was mostly enriched in the fat body rather than in other tissues. Knockdown of enhanced proliferation, whereas overexpression of inhibited its proliferation. Furthermore, we confirmed that increased the expression of the and in the JAK-STAT immune pathway and inhibited proliferation. Taken together, our current findings demonstrate that inhibits proliferation by promoting the JAK-STAT pathway through increased expression of and . This study provides new insights into the complicated connections among microsporidia pathogens, LD surface proteins, and insect immunity.IMPORTANCELipid droplets (LDs) are lipid storage sites in cells and are present in almost all animals. Many studies have found that LDs may play a role in host resistance to pathogens and are closely related to innate immunity. The present study found that a surface protein of insect lipid droplets could not only regulate the morphological changes of lipid droplets but also inhibit the proliferation of a microsporidian pathogen () by activating the JAK-STAT signaling pathway. This is the first discovery of the relationship between microsporidian pathogen and insect lipid surface protein perilipin and insect immunity.