Following baculovirus infection, the level of host messenger RNA (mRNA) declines and the synthesis of host proteins is shutoff in virus-infected cells. To comprehensively understand the regulation of host gene expression by Bombyx mori nucleopolyhedrovirus (BmNPV), we took a complementary DNA (cDNA) subtraction approach. Northern blot analysis was then performed to confirm whether obtained clones are differentially expressed. From these analyses, we obtained 4 down-, 7 up- and 2 non-regulated host gene candidates during the early stage of infection. Sequence analyses showed that these may encode proteins involved in transcription, cell cycle, cell adhesion, protein degradation, apoptosis or energy metabolism. We then measured the ADP/ATP ratio to address the response of host energy metabolism upon baculovirus infection. The ADP/ATP ratio showed cell death-like rapid increase following BmNPV infection with a transient decrease during 12–24 h post-infection (p.i.). Taken together, our results suggest that general events in host cells are controlled at the level of mRNA expression by BmNPV infection.