The spore-forming bacterium Bacillus thuringiensis (Bt) of B. cereus group uses toxin-opened breaches at the insect midgut epithelium to infest the haemolymph where it rapidly propagates despite antimicrobial host defences to induce eventually host death by acute septicaemia. The response of Bt to haemolymph and the latter’s role in bacterial pathogenesis is an area that needs clarification. We report the proteome analysis of Bt subsp. kurstaki (Btk) haemolymph stimulon consisted of significant changes in 60 (34 up- and 26 down-regulated) differentially accumulated proteins (DAPs). Gene Ontology (GO) enrichment analysis revealed Btk haemolymph-responsive DAPs were mainly involved in glutamate metabolism, transketolase activity and ATP-dependent transmembrane transporters. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis disclosed that DAPs were highly enriched in enzymes related to the biosynthesis of ansamycins, a family of bacterial polyketides with antimicrobial activity. Interestingly, around 30% of DAPs were putative virulence factors, including polyketide synthase, ABC transporter, and cytotoxin. Collectively, our findings suggest Btk haemolymph stimulon could be partially driven bacterial survival and propagation within the haemolymph of infected insects, contributing to its remarkable success as entomopathogen.