Upon treatment with recombinant Lcn2 in vitro, LPS-stimulated primary KCs produced less TNF-α and CCL2, and the activation of HSCs was suppressed by co-culture with rLcn2-treated KCs. The mechanism of splenic protection against liver fibrosis development may involve the splenic Lcn2. This evidence concerns the gene LCN2 and Hepatic fibrosis.