ZIKV causes microcephaly by crossing the placental barrier, however, the mechanism of trans-placental dissemination of ZIKV remains unknown. Here, we sought to determine whether monocytes, which can cross tissue barriers, assist ZIKV dissemination to the fetus. We determined this by infecting monocytes with two strains of ZIKV: South American (PRVABC59) and Nigerian (IBH30656) and analyzing viral replication. We found that ZIKV infects and replicates in monocytes and macrophages, which results in the modulation of a large number of cellular genes. Analysis of these genes identified multiple pathways including inflammasome to be targeted by ZIKV, which was confirmed by analyzing the transcript levels of the proteins of inflammasome pathways, NLRP3, ASC, caspase 1, IL-1 and IL-18. Interestingly, IFNα and the IFN inducible gene, MxA were not enhanced, suggesting prevention of innate antiviral defense by ZIKV. Also, inhibition of inflammasome led to an increased transcriptional activity of IFNα, MxA and CXCL10. Based on these results we suggest that ZIKV transcription is regulated by inflammasomes.