Perfluorooctanesulfonic acid (PFOS), a legacy member of the per- and polyfluoroalkyl (PFAS) chemical class, has been shown to broadly affect organ systems using unknown or multifaceted mechanisms. Epidemiological studies demonstrate that PFOS crosses the placenta and is found in breast milk, underscoring the importance of studying developmental exposure. Developmental PFOS exposure in zebrafish has been shown to affect both the endocrine and exocrine pancreas. This dissertation identifies and investigates factors that contribute to pancreatic toxicity with developmental PFOS exposure. The endocrine pancreas is composed of islets of Langerhans containing insulin producing β-cells that regulate blood glucose while the exocrine pancreas secretes digestive enzymes to break down nutrients for intestinal absorption. Due to its structure, PFOS has been identified as a fatty acid mimic, aiding in its ability to enter cells through nutrient transporters. Here we compare the effects of PFOS and a non-fluorinated structural analog alpha lipoic acid (ALA). We demonstrate that, like PFOS, ALA reduce islet area and alters lipid parameters, indicating that that fatty acid mimicry plays a role in islet toxicity with exposure to ALA and PFOS during development. We also investigate how PFOS exposure affects the development and function of the exocrine pancreas across multiple larval stages. We show that increased yolk utilization can lead to an insurmountable nutrient deficit, leading to reduced exocrine pancreas size in post-yolk feeding larvae. Additionally, we show that even at a timepoint and PFOS concentration where there are no detectable changes to the size of the exocrine pancreas, there is reduced exocrine pancreas function. Finally, we study how PFOS exposure affects islet vascularization where we saw a decrease in contact between the vasculature and the β-cells, likely driven by changes to cell-cell adhesion, namely reduced integrin gene expression with PFOS exposure. This dissertation advances the understanding of contributors to pancreatic toxicity with PFOS exposure. Future studies should be focused on studying the mechanisms underlying the processes described in this work to better understand the contribution of PFOS exposure during development on the risk of chronic diseases later in life.