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Skin color is determined by the amount of melanin and tyrosinase is a key enzyme of melanin synthesis. MITF(Microphthalmia-associated transcription factor) belongs to the basic helix-loop-helix-zip family of transcription factors and is the major regulator of tyrosinase and the related enzymes(TRPs). To screen depigmenting agents by HTS(high-throughput screening) system, we constructed a protein chip containing MITF. Since many compounds have low solubility in water they need to be dissolved in an organic solvent. However, the toxicity of organic solvents used in bioassays had not yet been fully documentated. Therefore, seven solvents (MeOH, EtOH, Acetone, Acetic acid, Iso propyl alcohol, tetrahydrofuran, DMSO) were chosen tested for their effects on bioassays such as cell viability(MTT), melanin assay, and protein chip. To search for the best solvent among them, a cell toxicity assay was performed by MTT. A crystal violet assay in the solvent-treated B16 mouse melanoma cells was also performed. the effect of organic solvents on melanin synthesis was investigated. In conclusion, less than 0.5% of DMSO is the best solvent which can be used in protein chip and bioassay.