?Introduction? Resolvin E3 (RvE3) is one of the lipid mediators E series Resolvin (RvEs) derived from EPA, an ?3 polyunsaturated fatty acid, which is produced in vivo and has the property of resolution of inflammatory responses. Rapid resolution of inflammation is important for maintaining homeostasis and macrophages play a central role during the inflammatory resolution phase. During the process of inflammatory resolution, macrophages produce the fibrogenic factor TGF-?1. Although many anti-inflammatory effects of RvEs have been reported in recent years, their anti-fibrotic effects and mechanism remain unclear. We have previously obtained the results from experiments using a mouse model of bleomycin-induced pulmonary fibrosis and mouse macrophage cell lines, which showed that among the RvEs (RvE1, RvE2 ,and RvE3), RvE3 may have greater activity as an anti-fibrotic agent. In the present study, we focused on RvE3 and attempted to elucidate the mechanism of its antifibrotic action. ?Aims?We aim to examine the effect of RvE3 on signaling pathways involved in fibrogenesis.?Methods?RAW264.7 cells were cultured to 80% confluence, stimulated with LPS at 0.1 µg/mL, then treated with RvE3 at 100 nM, cell lysates were collected and phosphorylation of each factor was examined by Western blotting.?Results?RvE3 inhibited phosphorylation of p38-MAPK and CREB which were activated by LPS stimulation. ?Conclusions?Phosphorylation of p38-MAPK has been implicated in TGF-?1-induced epithelial-mesenchymal transition, suggesting that RvE3 may have an anti-fibrotic effect by acting on the p38 MAPK signaling pathway in macrophages, thereby suppressing TGF-?1 production.