Corticosteroids are increasingly being used during the peri-implantation period to treat women with repeated IVF failure and recurrent miscarriage. However, the direct effects of prednisolone (PRDL), one of the commonly used corticosteroids on early embryo development is not understood. To mimic the possible clinical scenario and to understand the embryonic response to direct PRDL exposure, this pilot study was conducted in a mouse model. Cleavage stage embryos exposed to 3 and 30µM PRDL in vitro were assessed for peri-implantation developmental potential, genetic integrity, inner cell mass (ICM) proliferation and pluripotency markers in the proliferated ICM cells. Exposure to 30µM PRDL delayed the embryonic progression beyond compaction (P<0.05) in comparison to vehicle control and, had reduced total cell number (P<0.001) than all other groups. In addition, 30µM PRDL exposure resulted in poor hatching potential (P<0.05) and increased apoptosis in blastocysts (P<0.05) compared to 3µM PRDL. On the other hand, completely formed ICM outgrowths were significantly higher (P<0.05) in 3µM PRDL compared to control. However, no significant differences were observed in the expression of pluripotency genes. In conclusion, the trend observed in embryos exposed to PRDL in vitro provides important information concerning the use of this drug when treating patients at the peri-implantation phase of IVF cycles. However, the clinical value of this observation on human embryo development needs further research.