TIPE2, the tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TNFAIP8L2), plays an important role in regulating inflammation and immune homeostasis. Recent studies discovered that TIPE-2 involved in the development of several tumors and other proliferative diseases. The purpose of this study was to explore the function of TIPE-2 in the activation and proliferation in HSC-T6 cells. Our study showed low expression of TIPE-2 in primary HSCs from CCI4-treated mice and activated HSC-T6 cells. Functionally, over-expression of TIPE-2 by GV141-T1PE-2 hindered the HSC-T6 cells activation and proliferation and expressions of beta-Catenin, Cmyc, Cyclin Dl. However, inhibition TIPE-2 expression by TIPE-2 siRNA showed the opposite effect. These observations revealed that TIPE-2 held a protective effect on liver fibrosis and could be a potential therapeutic target. (C) 2017 Published by Elsevier Inc.