Previous studies have shown that shikonin(SHI), the bioactive naphthoquinone constituent extracted from Chinese herb Lithospermum Erythrorhizon, possesses the potential to confront inflammation, and has little concerns towards drug residues comparing with antibiotics. While mastitis in dairy industry always trigger great harm to milk yields, effects of SHI on lipopolysaccharides (LPS)-induced mastitis should be measured. Here, we demonstrate anti-inflammatory effects of SHI on LPS-challenged mastitis and elucidate the potential signaling pathway both in vivo and in vitro. As a result, SHI administration mice significantly suffered less impairment of mammary gland and less recruitment of neutrophils than LPS administration mice. SHI significantly suppressed the expression of p-I kappa B alpha and p-p65, which are the critical proteins functioning in NF-kappa B signaling pathway. qPCR results indicate decreasing level of upstream pro-inflammatory cytokines in tissues, such as TNE-alpha, IL-1 beta, and IL-6. The results are corresponding with the results in vitro, suggesting the potential usage of SHI as a therapeutic medicine in mastitis. (C) 2018 Published by Elsevier Inc.