To investigate the effect of single nucleotide polymorphisms (SNP) 45 and 276 of the adiponectin gene on non-alcoholic fatty liver disease (NAFLD) with or without metabolic syndrome.A total of 165 NAFLD, 83 NAFLD with metabolic syndrome and 160 healthy controls from Chinese population were genotyped for the adiponectin gene (+45T>G and +276G>T) by PCR-restriction fragment length polymorphism methods. Plasma adiponectin and insulin levels were determined by enzyme-linked immunosorbent assay and radioimmunoassay, respectively. Insulin resistance (IR) was evaluated by using homeostasis model assessment of IR (HOMA-IR).NAFLD with metabolic syndrome had further extent of IR and hypoadiponectinemia. No association of SNP45 or SNP276 was found in NAFLD or NAFLD with metabolic syndrome. Subjects carrying the G allele of SNP45 showed higher levels of triglyceride (TG), fasting blood sugar (FBS), HOMA, body mass index (BMI), and alanine transaminase (ALT), as well as lower plasma adiponectin levels. In the normal-weight group of SNP276, subjects carrying the G allele showed higher HOMA and subjects carrying the T allele showed lower BMI.Our study observed further hypoadiponectinemia and IR in NAFLD with metabolic syndrome. The T45G and G276T of the adiponectin gene may not be the important determinants of NAFLD in Chinese people, but some of them still influence serum ALT, BMI, IR, lipid, glucose metabolism and plasma adiponectin concentration.