Eosinophilic cell lines, HL-60 clone 15 cells and EoL-1 cells, have contributed to clarifying the mechanisms responsible for differentiation into eosinophils. These cells differentiate into eosinophils by continuous histone acetylation. Histone deacetylase inhibitors, sodium butyrate and apicidin, promote the transactivation of various genes in these cells by causing the hyperacetylation of histones, resulting in the differentiation of cells into eosinophils. In contrast, transient acetylation by histone deacetylase inhibitors such as trichostatin A does not induce eosinophilic differentiation. This chapter describes the maintenance of HL-60 clone 15 cells and EoL-1 cells and induction of the differentiation of these cell lines into eosinophils by the histone deacetylase inhibitor sodium butyrate.