Objective To investigate the effects and mechanism of retinoie acid on B16 marina mel-anoma cells and human melanocytes in vitro. Methods B16F10 murine melanoma cells and human mela-noeytes were cultured in culture medium which contains different concentration of components, including retinoic acid. Using reverse transcription-polymerase chain reaction (RT-PCR) mRNA expression of the tyrosinase was detected. Tyrosinase activity, melanin content and cell proliferation rate were also deter-mined. Results Retinoieacid exhibited an inhibitory effect on the expression of tyrosinase mRNA. As the concentration of retinoic acid was 100 μmol/L, treating for 72 h, the expression of tyrosinase mRNA de-creased 30.13 %, retinoic acid exhibited an inhibitory effect on tyrosinase activity and melanin production at high concentration (>500 μmol/L), and it could promote the cell proliferation. Retinoic acid and hy-droqninone could be cooperative at high concentration (1 000 μmol/L), and enhanced the down regulation of tyrosinase activity and melanin content. Retinoic acid could also mitigate the inhibitory effect of hydro-quinone on cell proliferation, so as to protect the cells from injury. Hydroquinone had no effect on tyrosi-nase gene expression at mRNA level. Conclusion Retinoic acid inhibits the synthesis of melanin by the genetic regulation at mRNA level.