Objective To investigate the effect of retinoic acid(RA) on cell apoptosis and gene regulation of insulin-like growth factor binding protein 6(IGFBP-6) in rat chondrocyte.Methods Chondrocyte from rat were cultured with all trans retinoic acid(ATRA) at 1×10~(-6) mol/L for 24 hours.The cell immunochemistry method and flow cytometry were used to measure the 2-collagenous and the cell apoptosis in ATRA-treated chondrocyte;The IGFBP-6 mRNA and protein level in chondrocyte were detected by Reverse Transcription Polymerase Chain Reaction(RT-PCR) and Western blotting analysis.Results The 2-collagenous in chondrocyte were down-regulated by ATRA at 1×10~(-6) mol/L.The cell apoptosis in chondrocyte exposed to ATRA at 1×10~(-6) mol/L increased 250%,compared with control group (P0.05).The IGFBP-6 mRNA and protein level in ATRA-treated chondrocyte were increased 128% and 195%,respectively(P0.05).Conclusion Retinoic acid may be down-regulated the secretion and cell proliferation,but up-regulated the cell apoptosis of chondrocyte in vitro.Retinoic acid may possess the up-regulation on cell apoptosis through the effect on genetic transcription and translation of IGFBP-6.