OBJECTIVE To investigate the inhibition of proliferation of retinoblastoma cells (SO-Rb50) and the differentiation of tumor cells into normal cell types by all trans retinoic acid (ATRA). METHODS This was an experimental study. SO-Rb 50 cells were treated with ATRA at different concentrations and growth curves were plotted. IC50 was analyzed by MTI method. Cell cycles before and after drug treatment were analyzed using flow cytometry. Morphologic characters of living cells and hematoxylin and eosin (HE) stained cells were observed microscopically before and 20 days after drug treatment The cell markers of NSE, vimentin, GFAP were detected with immunohistochemical method before and 20 days after drug treatment. RESULTS Cell growth was inhibited by ATRA treatment dose-dependently from 0 to 1 x 10(-5) mol/L and the cell viability was decreased. The IC50 of ATRA measured by MTT was approximately 14.05 microm/L. Treated with 1 x 10(-5) mol/L ATRA, the G0/G1 stage cells increased from 56.5% before treatment to 66.6%-81.0% after treatment, whilst S stage cells decreased from 33.1% to 22.3%-15.9%. Cells could attach to poly-lysine coated cover slides and formed small colonies. Some cells changed from round in shape to oval or fusiform shapes. The ratio of nuclear to cytoplasm decreased after the treatment of ATRA. Some cells extended long or short processes 20 days after treatment. Immunohistochemical studies showed that cells were stained moderately positive, strongly positive and weakly positive by NSE, vimentin and GFAP antibodies, respectively before treatment. After the ATRA treatment, cells were stained strongly positive, strongly positive and moderately positive by NSE, vimentin and GFAP antibodies, respectively. CONCLUSIONS ATRA significantly inhibits the proliferation of SO-Rb 50 cells and cells arrested at G0/G1 stage of cell cycle. ATRA induces differentiation of retinoblastoma cells towards the neurons and gliocytes.