Adenosine deaminase acting on RNA (ADAR) enzymes, ADAR1 and ADAR2, mediates adenosine-to-inosine RNA editing, and their mRNA expressions are altered during developmental, physiological, and pathophysiological processes in the nervous system. The present study attempted to investigate the involvement of epigenetic modifying enzymes, such as DNA methyltransferase (DNMT) and histone deacetylase (HDAC), in the regulation of ADAR1 and ADAR2 mRNA expressions in neuronal cells. Using human neuronal SH-SY5Y cells, we found that the DNMT inhibitor 5-aza-2'-deoxycytidine led to an increase in ADAR2, but not ADAR1, mRNA expression in a concentration-dependent and time-dependent manner. However, treatment with HDAC inhibitor trichostatin A elicited an increase in ADAR2 mRNA expression and a decrease in ADAR1 mRNA expression, and these changes were blocked by actinomycin D, a transcription inhibitor. Taken together, these findings suggest that ADAR1 and ADAR2 expressions are subject to different regulations by DNMT and HDAC enzymes in neuronal SH-SY5Y cells.