Transplantation of the pancreatic islets of Langerhans (islets) is a promising cell therapy for treating insulin-dependent type 1 diabetes mellitus. Islet transplantation is a minimally-invasive technique involving relatively simple surgery. However, after intraportal transplantation, the transplanted islets are attacked by the recipient’s immune system, because they activate a number of systems, including coagulation, complement response, inflammation, immune rejection, and recurrence of autoimmune disease. We have developed a surface modification and microencapsulation technique that protects cells and islets with biomaterials and bioactive substances, which may be useful in clinical settings. This approach employs amphiphilic polymers, which can interact with lipid bilayer membranes, without increasing cell volume. Molecules attached to these polymers can protect transplanted cells and islets from attack by the host immune system. We expect that this surface modification technique will improve graft survival in clinical islet transplantation.