The differentially expressed microRNAs (miRs) in pregnancy-related complications have not been completely clarified. In this study, we used a nonbiased microarray approach to identify circulating miRs in maternal whole peripheral blood. Moreover, the role of post-translational regulatory mechanism of miRs in preeclampsia (PE) was investigated. Plasma and placental tissue samples were collected from 26 pregnant women who went on to develop PE and 18 healthy control subjects, and then miRs expression profiles in plasma, mRNA and protein expression of v-ets erythroblastosis virus E26 oncogene homolog 1 (ETS-1) were measured by real-time RT-PCR and western blotting analysis in plasma and placenta samples. From the microarray, we identified the expression of miR-300 showed the highest level of all the miRs, miR-300 was significantly increased in the peripheral blood form PE patients as compared to healthy control subjects. The trend for increase in miR-300 expression was mirrored within placental tissue from PE patients compared with healthy controls. In parallel, ETS-1 as a target gene could be regulated by miR-300 by targeting its 3'-UTR. Moreover, both mRNA and protein expression of ETS-1 were markedly decreased in placental tissue from PE patients compared with healthy controls. Furthermore, the association between the miR-300 levels and ETS-1 mRNA expression in placental tissue from all participants was further confirmed by linear regression analysis. The result demonstrated that miR-300 levels were significantly and negatively correlated with ETS-1 mRNA expression in placental tissue. In conclusion, miR-300 was reported to serve as an improved bio-marker for PE screening, and we had identified ETS-1 as a target gene that could be regulated by miR-300.