Aim To investigate the relationship of variable number of tandem repeat(VNTR) polymorphism in intron 2 of interleukin-1 receptor antagonist(IL-1Ra)gene and serum IL-1Ra levels with coronary heart disease. Methods 245 coronary heart disease patients and 236 normal subjects were recruited in the study. Their VNTR polymorphisms of IL-1Ra gene were analyzed using polymerase chain reaction method and their serum IL-1Ra levels were measured using enzyme-linked immunosorbent assay. Results There were four kinds of genotype: Ⅰ/Ⅰ, Ⅰ/Ⅱ, Ⅰ/Ⅳ and Ⅱ/Ⅱ. The frequencies of the four genotypes were as follows:Ⅰ/Ⅰ,88. 6%;Ⅰ/Ⅱ,9.8%;Ⅰ/Ⅳ,1.2%;Ⅱ/Ⅱ,0.4% in coronary heart disease patients andⅠ/Ⅰ,80.1%;Ⅰ/Ⅱ,16.9%;Ⅰ/Ⅳ,2.1%;Ⅱ/Ⅱ,0.9% in normal subjects, respectively. The frequency of alleleⅡ was significantly lower in coronary heart disease patients, than that in normal controls(5.3% and 9.3%, respectively),which is more significant in myocardial infarction patients and angina patients(4.3% and 15.6%, respectively). In coronary heart disease patients, the serum IL-1Ra levels in allele Ⅱ carriers were significantly higher than in no allele Ⅱcarriers. Conclusion The VNTR polymorphism of IL-1Ra gene may affect serum IL-1Ra levels, and may play a protective role in the development of coronary heart disease.