The application of baculovirus as a gene delivery vector for mammalian cells is limited by gene silencing in host cells. Although histone deacetylation inhibitors were known to improve baculovirus-mediated gene expression in mammalian cells, another group of chemicals that induces epigenetic changes, DNA methyltransferase inhibitors (DNMTis), were reported to have no such effect. In the current work, we found that, when added prior to virus inoculation, DNMTis improved baculovirus-mediated gene expression by fourfold or more in all four mammalian cell lines tested. The presence of inhibitors during the period of virus inoculation was important for them to be effective.