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This study was to discuss the relationship among the change in the activity of Bombyx mori carboxylesterase (BmCarE)in the midguts, the differential expression of BmCarE gene (bmcare) in the midguts, and the ability of Bombyx mori resistant to densonucleosis virus (BmDNV), and to elucidate the molecular mechanism of resistance to BmDNV-Z. With two silkworm strains, HUABA, which is susceptible to BmDNV-Z, and BC8 (a near isogenic line of HUABA), which is completely resistant to the same virus, as materials, the activity of BmCarE in the midgut was determined by Bio-Tek Synergy, and the differential expression of bmcare between the two strains was investigated by real-time fluorescence quantitative PCR, both at 12, 36, and 72 h post oral inoculation of the two strains with virus (hereafter referred as inoculation). While the activity of BmCarE in the midguts of BC8 inoculation group at 12 h post inoculation was higher than that in the BC8 control group, the HUABA inoculated group, and the HUABA control group by 3.28, 2.26, and 3.02times, respectively, with the difference being highly significant (P＜0.01), there was no statistical difference among the other groups. The relative expression level of bmcare in the midguts of BC8 inoculation group at 12 h post inoculation was higher than that in the BC8 control group, the HUABA inoculation group, and the HUABA control group by 17.714, 21.76,and 15.09 times, respectively, with the difference being highly significant (P ＜ 0.01), and there was no statistical difference among other groups. The elevation of BmCarE activity and expression level of bmcare in the resistant strain at 12 h post inoculation may relate to the resistant gene (nsd/nsd) and the stimulation of BmDNV-Z. The molecular basis for the elevation of BmCarE activity in the resistant strain BCs may be the change in the expression level of bmcare.