Estrogen is important in the pathogenesis of systemic lupus erythematosus (SLE). The modulation of estrogen on dendritic cells (DCs) may involve in SLE development. Our purpose was to find out whether in vitro the effect of estrogen on DCs is correlated with the disease progression in vivo. We compared the effects of 17beta-estradiol (E2) on spleen DCs from SLE murine model-(NZB x NZW) F1 female mice before and after the disease onset. Results showed that E2 changed the surface molecule CD40, cytokines IL-6, IL-10, IL-12 and TNFalpha and stimulatory ability of spleen DCs from the mice. Selective estrogen receptor modulator-tamoxifen (TAM) could antagonize E2 effects and E2 could influence estrogen receptor (ER alpha) level in DCs. The changes of DCs from various age old mice were different even contrast. So E2 participates in SLE through modulating DCs by binding ER alpha. The effects of E2 on DCs from mice in various disease progression stages were different.