A sulfonylurea with a polymerizable end group (a glyburide analogue) was synthesized. This monomer was copolymerized with N,N-dimethylacrylamide (DMAAm). In vitro bioactivity was evaluated by adding these sulfonylurea monomers and copolymers into normal rat islet cultures and measuring the insulin concentration in the supernatant. The sulfonylurea monomer showed a stimulatory effect on rat islets at glucose concentrations of 50 and 100 mg/dL, with equivalent stimulation indices for glyburide, the potent sulfonylurea drug, while no effect was observed at a glucose concentration of 200 mg/dL. The sulfonylurea polymer stimulated Langerhans islets to secrete insulin at a low glucose concentration of 50 mg/dL, with 80% bioactivity of its monomeric compound. However, at 100 and 200 mg/dL glucose concentrations, there was no significant stimulation in insulin secretion. Because it is suggested that the sulfonylurea receptors are located in the lipid phase on the ATP-sensitive K+ channels, the solubilization of sulfonylurea into, and its diffusion through, the lipid phase in the cell membrane may affect the interactions of sulfonylurea with its receptors. In the case of the sulfonylurea polymer, the sulfonylurea unit in the polymer can interact with its receptor as can be seen by the increased insulin secretion at a glucose concentration of 50 mg/dL, but its interaction would be interfered with to some extent by a large hydrophilic polymer backbone. Thus, less change in insulin secretion was observed at higher glucose concentrations by the addition of this particular sulfonylurea polymer.