Synthetic mRNA is becoming increasingly popular as an alternative to pDNA-based gene therapy. Currently, multiple synthetic mRNA platforms have been developed. In this study we investigated the expression kinetics and the changes in mRNA encoding cytokine and chemokine levels following intradermal electroporation in pigs of pDNA, self-replicating mRNA, and modified and unmodified mRNA. The self-replicating mRNA tended to induce the highest protein expression, followed by pDNA, modified mRNA, and unmodified mRNA. Interestingly, the self-replicating mRNA was able to maintain its high expression levels during at least 12 days. In contrast, the expression of pDNA and the nonreplicating mRNAs dropped after respectively one and two days. Six days after intradermal electroporation a dose-dependent expression was observed for all vectors. Again, also at lower doses, the self-replicating mRNA tended to show the highest expression. All the mRNA vectors, including the modified mRNA, induced elevated levels of mRNA encoding cytokines and chemokines in the porcine skin after intradermal electroporation, while no such response was noticed after intradermal electroporation of the pDNA vector.