All lepidopteran baculovirus genomes sequenced to date encode a viral fibroblast growth factor homolog (vFGF). Recently, we generated a Bombyx mori nucleopolyhedrovirus (BmNPV) mutant lacking functional vfgf and found that BmNPV vfgf contributes to virus virulence in B. mori larvae. However, the steps at which BmNPV vFGF works during in vivo virus infection were unclear. To uncover the role of vFGF during systemic infection of silkworm larvae, we generated a BmNPV mutant, BmIEGFP, possessing an ie-1 promoter-driven green fluorescent protein gene, and its derivative BmIEGFP/FGFD, in which vfgf was partially deleted from the genome of BmIEGFP. Intrahemocoelic and oral infection experiments using these viruses revealed that the loss of functional vFGF reduces viral infectivity in B. mori hemocytes. Our results suggest that BmNPV vFGF is required for efficient systemic infection, presumably by a chemotactic effect that allows budded virus to infect hemocytes efficiently.