Abstract: Objective To investigate the relationship between estrogen receptor gene polymorphism and SLE. Methods The polymorphism of estrogen receptor gene was detected using PCR-restricted fragment length polymorphism in 82 patients with SLE and normal human controls. Results The distribution of estrogen receptor gene polymorphism was similar in the male and female controls, and, ppxx and PpXx were the most common genotypes. The distribution difference of estrogen receptor gene polymorphism was significant between the female and male SLE patients. The frequency of PpXx was significantly higher in the male patients than in the female patients and normal male controls （66.6% vs 21.1%, 66.6% vs 16.7%, respectively, both P < 0.05）. The distribution difference of estrogen receptor gene polymorphism was of no significant difference between the female patients and normal female controls. Conclusions The distribution difference of estrogen receptor gene polymorphism is significant between the male and female SLE patients, and the frequency of PpXx in male SLE patients is higher than that in female SLE patients and normal male controls, which hints the genotype may correlate with the susceptibility of male patients with SLE.