The present study investigated the potential health-promoting effects of heat-inactivated Lactobacillus gasseri TMC0356 (TMC0356) on the metabolic syndrome (MS) and the probable mechanisms underlying these effects using an MS rat model. For the purpose of the study, sixty Sprague-Dawley rats were randomly divided into five groups: a control group fed a conventional diet, an MS model group fed a high-fat and high-salt (HFS) diet and three TMC0356 test groups (low-, medium- and high-dose groups) fed an HFS diet supplemented with TMC0356 at 41.8, 83.5 and 167.0 mg/kg body weight (BW) per d, respectively. Food intake and BW were measured weekly. Fasting blood glucose (FBG), lipid profiles and blood pressure (BP) were measured at 0, 5, 10 and 15 weeks. Organ coefficients, immune cell counts and serum insulin, adiponectin, C-reactive protein (CRP), IL-6, TNF-α, IgG and secretory IgA levels were measured at the 15th week after diet intervention. The HFS diet increased the BW, liver or fat:BW ratio, FBG, homeostatic model assessment of insulin resistance, adiponectin, serum LDL-cholesterol and total cholesterol levels and BP (P< 0.01). Average food and energy intakes in the three TMC0356 groups were significantly lower than those of the MS model group. All the metabolic indices, except BP, were markedly improved (P< 0.05) by oral administration of low and medium doses of TMC0356. The thymus index in the medium-dose group and lymphocyte, CRP, IL-6, TNF-α and IgG levels in all the three TMC0356 groups were significantly increased (P< 0.05 or P< 0.01) compared with those in the MS model group. These results suggest that TMC0356 can improve the metabolic characteristics of MS rats by suppressing appetite. Additionally, the enhancement of inflammatory immune response may be, at least in part, the mechanism underlying the health-promoting effects of TMC0356 on the MS.