Introduction: CD36 is a key protein involved in regulating the uptake and utilization of fatty-acids in heart and skeletal muscle. The aim of this study is to assess the association between rs10499859 A>G and rs13246513 C>T polymorphisms of CD36 gene and metabolic syndrome (MetS). Materials and Methods: In this case-control study, 140 subjects with MetS and 187 healthy ones were randomly selected from among the Tehran Lipid and Glucose Study population. Biochemical and anthropometrical variables were measured, and polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism. Results: Case and control groups did not differ in allele and genotype frequencies for these SNPs. Under a dominant model, A and T alleles of these SNPs were significantly associated with elevated levels of HDL-C, before age and sex adjustment (P 0.027 and 0.016 respectively). A allele carriers had significantly increased levels of BMI compared to G allele carriers after adjustment for MetS, and under the dominant model (P= 0.009). Presence of G allele was also significantly associated with increased diastolic blood pressure (P= 0.016) before adjustment for confounders, using a recessive model. Conclusion: The results of this study show that genetic variation of CD36 gene was associated with metabolic risk factors such as HDL-C and BMI. Although the effect of each SNP polymorphism  plays a small role, it depends specifically on their interaction with environmental factors.