The knock-in efficiency is very important to manipulate gene editing in the transgenic domestic animal. Recently, it is reported that transiently loosen nucleosome folding of transcriptionally inactive chromatin might have potential tp enhance the homologouse recombination efficiency. Histone deacetylases (HDAC) are a class of enzymes that remove acetyl groups from an amino acid on a histone. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. In this study, Mac-T cell were treated with 10uM VPA (valproic acid, HDAC inhibitor) for 24 h and transfected with Knock-in vector and TALEN at targeting of β-casein gene. After 3 day of transfection, knock-in efficiency was confirmed by PCR. The level of HDAC2 protein in Mac-T cells was decreased by VPA treatment. The knock-in efficiency in the Mac-T cell with treated HDAC inhibitor was higher than cell not treated HDAC inhibitor. These results indicated that chromatin modification by HDAC inhibitor enhances homologous recombination efficiency in the Mac-T cell.