The aim of this study was to investigate the effects of Callistephus chinensis flower (CCF) polyphones on symptoms of metabolic syndrome in a newly developed high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) mouse model. C57BL/6J mice were fed a high fat diet (HFD; 50% energy as fat) with normal drinking fluid or HFD with CCF polyphones (50 mg L(-1) or 100 mg L(-1)) in drinking fluid for 12 weeks. As a comparison, mice fed a normal-fat (NFD; 10% energy as fat) and with normal drinking fluid were also included. The HFD group developed more severe symptoms of metabolic syndrome than the NFD group. CCF polyphones treatment significantly reduced fecal lipids compared to the HFD group, suggesting a strong indication of improved lipid metabolism. Liver damage and liver triglyceride levels were also decreased by CCF polyphones treatment. Moreover, both morphologic and histological detections indicated that CCF polyphones significantly reversed HFD-induced hepatic steatosis and liver injury. Furthermore, CCF polyphones significantly ameliorated both HFD-induced metabolic disorders, such as insulin resistance, and inflammatory cytokines, including interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Moreover, hepatic peroxisome proliferator-activated receptor (PPARα) and the gene involved in PPARα, Peroxisomal acyl-CoA oxidase (ACOX), were markedly up-regulated at protein levels by CCF polyphones. Our results demonstrate that the HFD produces metabolic syndrome of NAFLD, and CCF polyphones treatment can alleviate these symptoms. The beneficial effects of CCF polyphones are associated with improved lipid metabolism and reduced levels of inflammatory cytokines.