A multidrug-resistant clone of human oral epidermoid carcinoma KB cells was isolated by stepwise selection on exposure to increasing doses of vincristine. The final clone, KBv200, obtained after ethylmethane sulfonate mutagenesis showed 156-fold higher resistance to vincristine than KB cells. The cells were also cross-resistant to paclitaxel and adriamycin. The aim of this study was to explore the reversal effect and potential mechanism of resveratrol on KBv200 cells. MTT assay was used to investigate the reversal index of resveratrol to vincristine, adriamycin and paclitaxel. Cell apoptosis was measured by flow cytometry. RT-PCR and western blot were used to detect mRNA and protein expression of multidrug-resistant gene MDR1 and apoptosis-suppressing gene Bcl-2. Resveratrol produced a synergistic effect combined with the chemotherapeutic agents and reversed the multidrug-resistant phenotype of KBv200 cells. Flow cytometry confirmed that the percentage of apoptotic cell increased when KBv200 cells were exposed to resveratrol. The results of gene detection showed that the expression levels of MDR1 and Bcl-2 were decreased upon resveratrol treatment. Resveratrol can efficiently reverse multidrug resistance in KBv200 cells. The potential mechanism may be via inhibiting the multidrug-resistant gene expressions and/or promoting cell apoptosis.