Female infertility is a heterogeneous disorder with a variety of complex causes, including inflammation and oxidative stress, which are also closely associated with the pathogenesis of polycystic ovary syndrome (PCOS). As a new treatment for PCOS, berberine (BER), a natural compound from Berberis, has been clinically applied recently. However, the mechanisms underlying the association between BER and embryogenesis are still largely unknown. In this study, effects of BER on preimplantation development were evaluated under both normal and inflammatory culture conditions induced by lipopolysaccharide (LPS) in mice. Our data first suggest that BER itself (25 nM) does not affect embryo quality or future developmental potency; however, it can effectively alleviate LPS-induced embryo damage by mitigating apoptosis via reactive oxygen species (ROS)-/caspase-3-dependent pathways and by suppressing proinflammatory cytokines via inhibition of the NF-kappaB signaling pathway during preimplantation embryonic development. In addition, skewed cell lineage specification in the inner cell mass (ICM) and primitive endoderm (PE) caused by LPS can also be successfully rescued with BER. In summary, these findings for the first time demonstrate the nontoxicity of low doses of BER and its antiapoptotic and antioxidative properties on embryonic cells during mammalian preimplantation development. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.