ZJUFT17 (T17) is a potential probiotic bacterium isolated from Chinese traditional sourdough. The purpose of this study was to investigate its weight-reducing effects in mice fed a high-fat diet (HFD) and further to elucidate possible mechanisms. Male C57BL/6J mice fed HFD were given T17 (2-4×10 cfu) intragastrically for 10 weeks. The results showed that the administration of T17 significantly suppressed HFD-induced body weight gain, alleviated HFD-induced increase in serum lipids and decreased energy intake. The serum levels of obesity-related metabolic signaling molecules, including insulin, adiponectin, lipopolysaccharide (LPS) and the cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α, were markedly improved. The 16S rRNA gene sequencing revealed that T17 administration dramatically modulated the gut microbiota, suppressing pathogenic and pro-inflammatory microbes and stimulating the microbes favoring anti-obesity. The weight-reducing efficacy of T17 may be explained by its ability to ameliorate systemic inflammation and insulin resistance mediated by gut microbiota. This study revealed that T17 could ameliorate obesity and the concomitant metabolic syndrome in mice and that the lactic acid bacteria in the sourdough ecosystem may also possess anti-obesity/weight-reducing properties.