AbstractBackgroundDiabetes is a group of diseases characterized by loss of β cell mass and/or function, resulting in hyperglycemia. With no established curative treatment, this has initiated research in β cell regeneration. Current animal models have either limited regenerative capacity (mice) or small size and evolutionary distance from humans (zebrafish). There is a need for new models to study endogenous regeneration pathways. This study proposes the axolotl salamander (Ambystoma mexicanum) as a model for studying the regeneration of β cells and aims to establish a protocol for STZ‐induced hyperglycemia to mimic a diabetic state.ResultsIn this pilot study, five streptozotocin (STZ) protocols were tested, and the most effective one was identified on the basis of glucose tolerance tests. Blood glucose levels were monitored to track both disease progression and remission. Histological examination of the pancreas and systemic effects of STZ treatment were also evaluated.ConclusionInduction of a diabetes‐like state (hyperglycemia) in axolotls was possible with STZ, but variability among animals suggests the need for a higher degree of normalization or larger sample sizes. Histological regeneration was not observed, though blood glucose levels normalized over time. Some STZ‐treated animals developed edema, but its cause remains unknown.