An efficient solid-phase protein refolding method based on artificial chaperone-assisted refolding is proposed. The method employs insoluble cyclodextrin polymer beads and the expanded-bed technique. a-Glucosidase, whose spontaneous refolding yield from a urea-denatured state is up to 30% at a protein concentration of up to 10 mug/ml, could be refolded with a yield that was improved more than two-fold at a protein concentration more than five-fold higher when protein solution was circulated through an expanded bed under optimized conditions. Unlike the conventional liquid-phase artificial chaperone system, further steps to purify the refolded product, which are generally needed to remove detergent-cyclodextrin complex and excess cyclodextrin, were unnecessary. In addition, the polymer beads were reusable after simple washing with water, and the continuous system is suitable for easy scale-up using commercially available devices. This new method is considered to be a powerful means of achieving large-scale protein refolding for industrial protein production.