The cure for type 1 diabetes (T1D) will require either the replacement or regeneration of insulin-producing cells, together with measures that prevent their immune-mediated destruction. Experiments in rodent models have found that pancreatic stem cells, committed progenitors and replicating beta-cells can all contribute to insulin-producing cell regeneration. The cellular and molecular mechanisms of these cells, both in vitro and in vivo, have been investigated by us and by others. Furthermore, our surgical research laboratory has developed a unique in vivo chamber model of T1D, allowing the assessment of the behaviour of different sources of insulin-producing cells with a view to their potential use in cell-based therapies.