Suppressor of cytokine signaling-3 (SOCS-3) plays an important role in negative regulation of inflammatory response. Evidence has shown that SOCS-3 and IL-10 expressions were significantly reduced in placental trophoblasts from preeclampsia. IL-10 is an anti-inflammatory cytokine. In this study, we sought to determine if enhance SOCS-3 expression could affect IL-10 production in placental trophoblasts. Placental JEG-3 cells were used. Over-expression of SOCS-3 was generated by transfection of JEG-3 cells with a green fluorescent protein (GFP) tagged SOCS-3 gene, SOCS-3/ZsGreen1, by siPORT lipid transfection. Cells transfected with ZsGreen1 vector only was used as control. Our results showed that IL-6 production was reduced in cells over-expressed with SOCS-3. Moreover, SOCS-3 transfected cells produced more IL-10 when stimulated with IL-6. The increased IL-10 production by JEG-3 cells was in a dose-dependent manner, p<0.05. Our data suggested that enhanced SOCS-3 gene expression could promote IL-10 production by placental trophoblast cells, suggesting that SOCS-3 may play an important role in regulation of cytokine induced anti-inflammatory response in placental trophoblasts.