Abstract: Objective To investigates the association of the ER22/23EK polymorphism of the glucocorticoid receptor gene (GR) with natural longevity in the XinJiang Uygur nationality people and the difference between the races. Methods 191 healthy individuals over 90 years old from Uighur people were recruited as the longevity group and 53 ages 65-70, matched in nationality, gender and region, formed the control group; at the same time, 82 Han nationality people aged between 65-70 who immigrated in Xinjiang Hetian more than 30 years ago were randomly selected and investigated. Genotyping was performed by using PCR-SSP, PCR-RELP and PCR-sequencing. Results The frequencies of ER22/23EK alleles and genotypes showed no significant difference between the longevity group and the controls in Uygur, but the carriers of ER22/23EK of GR gene in Xinjiang Han old folks were significantly more than those in Uygurs, the frequencies of WM, MM genotypes and M allele were significantly higher in Han nationality, while the frequencies of WW genotype and W allele were significant lower. Conclusion There is possibly no association between ER22/23EK polymorphism and XinJiang Uygur natural longevity, but there are significant differences between two ethnic groups.