Abstract: OBJECTIVE To study the protective effect of polysaccharide from antrodia camphorata on nonalcoholic fatty liver disease (NAFLD) in mice by regulatory T-cell (Treg) controled. METHODS The model of NAFLD mice was established by high fat diet, and setted up the control group, model group, low dose group and high dose group. The proportion of Treg cells in peripheral blood were detected by flow cytometry and detect the expression of alanine aminotransferase (ALT), aspartate aminotransferase (AST), transforming growth factor beta (TGF-β) and interleukin-6 (IL-6) expression in 1-4 weeks. After 4 weeks, the mice were killed and the liver was stained with oil red staining. The expression of TGF-β, Foxp3 and Smad3 proteins in liver tissue were detected by Western blot. RT-qPCR was used to detect the mRNA expression of IL-6, TGF-b, Foxp3 and Smad3. RESULTS NAFLD mice model was successfully constructed after 4 weeks fed with high fat diet, and the proportion of Treg in model group was significantly lower than that in control group(P<0.05). Compared with the model group, the proportion of Treg increased significantly(P<0.05). The liver function of mice was significantly improved. The expression of TGF-β increased and IL-6 decreased in peripheral blood. The levels of TGF-β, Foxp3, Smad3 mRNA were up-regulated in liver tissues, whereas the expression of IL-6 mRNA was down. CONCLUSION The polysaccharide from antrodia camphorata can protect NAFLD via Treg and TGF-β-Smad3 signal pathway. The mechanism of action is related to immune improvement.