Chemokines play an important role in the physiology and pathophysiology of acute and chronic inflammatory processes. We investigated whether chemokines such as RANTES (regulated upon activation, normally T cell expressed and secreted) promoter and monocyte chemoattractant protein-1 (MCP-1) regulatory polymorphisms were associated with systemic lupus erythematosus (SLE) in Chinese children.Forty-six patients with SLE and 107 healthy children of comparable ages were studied for genotypes with polymerase chain reaction-based assays.The frequency and distribution of genotypes of the -28(C/G) RANTES gene polymorphism were significantly different between the 2 groups (p < 0.001), and the RANTES -28G allele was significantly more frequent in patients with SLE than in healthy controls (23.9% vs 11%; p = 0.006, OR 2.37, 95% CI 1.25-4.28). There was no significant difference in the frequency or in the distribution of genotypes of the -2518(A/G) MCP-1 and the -403(G/A) RANTES gene polymorphisms between patients and controls (p = 0.32 and p = 0.19, respectively). The RANTES -28G allele was also significantly associated with higher initial levels of antinuclear antibody, lower levels of C3, and higher incidences of central nervous system lupus.In the Chinese population, children with RANTES -28C/G polymorphisms have increased risk of developing SLE. Healthy controls with the C/G or G/G genotype were 2.37 times more likely to have SLE compared to those with the C/C genotype.