Various stresses (high temperature, starvation, or sublethal Cryptococcal infection) increased the susceptibility of silkworms to bacterial infection by up to 100-fold, confirming the stress-induced immunosuppression reported in a range of species. When the silkworm was injected with a steroidal drug, betamethasone (1 mg/larva), the susceptibility of the silkworm to bacterial infection increased about 100-fold. This indicates that the immune function of the silkworm can be suppressed by a known compound that shows immunosuppressive effects in humans. We further tested the immunosuppressive effect of the culture supernatants (acetone extracts) of soil bacteria, and 24 out of 193 isolates showed the immunosuppressive activity. These results suggest that it is possible to search for immunosuppressive agents targeting innate immunity by using a silkworm bacterial infection model as a screening system, and that there may be candidate compounds for immunosuppressive agents among the substances produced by soil bacteria.