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Rat primary hepatocytes were exposed to positive reference compounds [cyclosporine A (CsA), clofibrate (CFR), tetracycline (TC), valproic acid (VPA), carbon tetrachloride (CCl4), tamoxifen (TMX)] in the presence of BODIPY558\/568 C<jats:sub>12<\/jats:sub>. The formation of fluorsecent particles or lipid droplets in the cytoplasm was confirmed by confocal laser scanning microscopy and electron microscopy respectively. The accumulation of BODIPY558\/568 C<jats:sub>12<\/jats:sub> was measured by fluorometry and high content imaging method. All positive reference compounds increased fluorescent particles in number and fluorescence intensity. High content imaging was more sensitive and selective method than fluorometry to detect fluorescent particles. Gene expression analysis of the hepatocytes showed two patterns: genes related to lipid metabolism\/synthesis were down\u2010regulated by oxidative stress inducing compounds: CsA, TC and TMX, and up\u2010regulated by peroxisome proliferator\u2010activated receptor\u2010alpha agonists: CFR and VPA. From these findings, we concluded that the cell\u2010based assay developed in this study is an appropriate method to predict drugs' potential for hepatosteatosis, and gene expression analysis is useful to profile the mechanism of the hepatosteatosis. 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