β-glucan has been shown to increase non-specific immunity and resistance against infections or pathogenic bacteria in several fish species, but information regarding its trans-generational immune-enhancing effects is still rather limited. Lysozyme is a maternal immune factor playing an important role in the developing embryos of zebrafish. Here we clearly showe that β-glucan enhanced the level of C-type lysozyme in eggs of zebrafish, and the embryos derived from β-glucan-treated zebrafish were more resistant to bacterial challenge than control embryos. Moreover, the transferred lysozyme was apparently linked with the antimicrobial defense of early embryos. In addition, we also showed that β-glucan induced a significant increase in the synthesis of C-type lysozyme in previtellogenetic oocytes. Therefore, we show for the first time that β-glucan can enhance the lysozyme level in offspring via both inducing the transfer of the molecule from mothers to eggs and stimulating its endogenous production in oocytes.