Ser/Thr protein phosphatase 2A (PP2A) is one of the type 2 protein phosphatases， which is required for many intracellular physiological processes and pathogen infection. However， the function of PP2A is unclear in silkworm， Bombyx mori. Here， we cloned and identified BmPP2A， a PP2A gene from B. mori， which has two HEAT domains and a high similarity to PP2A from other organisms. Our results showed that BmPP2A is localized in the cytoplasm and highly expressed in silkworm epidermis and midgut， and that Bombyx mori nucleopolyhedrovirus (BmNPV) infection induces down-regulation of BmPP2A expression. Furthermore， up-regulation of BmPP2A via overexpression significantly inhibited BmNPV multiplication. In contrast， down-regulation of BmPP2A via RNA interference and okadaic acid (a PP2A inhibitor) treatment allowed robust BmNPV replication. This is the first report of PP2A having an antiviral effect in silkworm and provides insights into the function of BmPP2A， a potential anti-BmNPV mechanism， and a possible target for the breeding of silkworm-resistant strains.