OBJECTIVE To investigate the effect of retinoic acid (RA) on cell apoptosis and gene regulation of IGF-2 in chondrocyte. METHODS One 1-month-old Chinese rabbit weighted 500 g was used in this experiment. The chondrocyte from rabbit knee were cultured by enzyme digestion. Twenty-five microL all-trans-retinoic acid (ATRA) (1 x 10(-6) mol/L) were added in the media of cultured chondrocyte for 24 hours as experimental group, while 25 microL DMEM were added as control group. The secretion of collagen II was observed by immunohistochemistry method, cell apoptosis was detected by flow cytometry, IGF-2 mRNA and protein expression in chondrocyte were detected by RT-PCR and Western blot analysis. RESULTS The expression of collagen II was down-regulated by ATRA in the experimental group. The cell apoptosis in chondrocyte exposed to ATRA at 1 x 10(-6) mol/L was 21% +/- 2%, which increased 5 times compared with the control group (5% +/- 1%). The IGF-2 mRNA and protein level in the experimental group were decreased 75% and 57%, respectively, compared to the control group. There were significant difference between the experimental group and control group in each index (P < 0.05). CONCLUSION RA may down-regulate the secretion and cell proliferation, but up-regulate the cell apoptosis in chondrocyte. The apoptotic effect may carry out through inhibiting the IGF-2 expression of chondrocyte.