OBJECTIVES: To examine the effects of orlistat and rosiglitazone and assess the changes of cardiovascular risk factors in a group of Chinese patients affected by the metabolic syndrome. METHODS: In a prospective, 6-months randomized single-blinded placebo-controlled study, 58 Chinese participants with type-2 diabetes or impaired glucose tolerance, aged > 18 years with a BMI of 23kg/m2 or above were administered orally 120 mg orlistat three times daily, rosiglitazone 2mg twice daily or placebo three times daily. Changes in clinical and metabolic parameters of the metabolic syndrome were monitored, including BMI, body fat, glycaemic control, lipid levels and drug tolerability. RESULTS: There were 20 individuals in the rosiglitazone group and 19 individuals in both the orlistat and placebo groups. There were statistically significant differences between the three groups in total cholesterol (p = 0.001), triglycerides (p = 0.037), LDL-cholesterol (p = 0.001), BMI (p = 0.001), hip (p = 0.002) and body fat (p = 0.006). The orlistat group demonstrated improved lipid profiles from baseline, especially on the reduction of total cholesterol (12% p = 0.0005) and LDL (21%, p = 0.0002). This was accompanied by improvements in the fasting insulin levels (p = 0.07) and Homeostatic Model Assessment (HOMA) scores (p = 0.026). In comparison, the rosiglitazone group exhibits maximum improvements in fasting insulin (p = 0.004), 2hr-post OGTT insulin (p = 0.004) and HOMA scores (p = 0.005). Although statistically insignificant, there is a slight increase from baseline in the LDL levels (12%) and body fat (3.7%). CONCLUSIONS: To prevent progression to type-2 diabetes mellitus and its complications, early detection and implementation of appropriate treatment strategies for the metabolic syndrome is crucial. Both rosiglitazone and orlistat appear to be promising in treating the metabolic syndrome.