Regulating immune homeostasis by targeting liver macrophage polarization is a potential therapeutic strategy for hepatic fibrosis. Chitooligosaccharide (COS) is a bioactive oligosaccharide possessing potent immunomodulatory and hepatoprotective effects. In this study the hepatoprotective effect of COS on hepatic fibrosis was examined in mice and the underlying mechanisms were investigated. Herein, mice were induced to hepatic fibrosis using carbon tetrachloride (CCl4) and concurrently treated with COS orally. Kupffer cells (KCs) were skewed towards M1 macrophage polarization by lipopolysaccharide (LPS) and towards M2 macrophage polarization by interleukin-4 (IL-4) in vitro, which were utilized for COS treatment. The results showed that mice were rescued from hepatic fibrosis by COS, marked by a reduction in the deposition of the extracellular matrix (ECM) and histological lesions. COS had an inhibitory effect on the polarization of M1 and M2 macrophages both in vivo and in vitro, characterized by the raised biomarker of the M1 and M2 macrophages slipping towards the basal levels. Furthermore, COS inhibited the JAK2/STAT1 pathways on M1 macrophages and the JAK1/STAT6 pathways on M2 macrophages in KCs. In summary, this study revealed a molecular mechanism for the impact of COS effectiveness on the polarization of liver macrophages, suggesting that is could be a possible intervention for hepatic fibrosis.