Objective(s): Arsenic is classified as a toxic metal that is naturally found in the Earth's crust, and long-term exposure to it can result in chronic human disorders like cancer and diabetes. Azelaic acid (AZA), a natural dicarboxylic acid, has been reported to have anti-oxidant and anti-inflammatory effects; hence, it may protect against the metabolic toxicity of arsenic. This study aimed to investigate whether AZA could ameliorate sodium arsenite (SA) toxicity toward rat islets of Langerhans. Materials and Methods: Pancreatic Islets of Langerhans isolated from adult male Wistar rats were divided into four groups of 10: control, SA, AZA, and SA plus AZA. Twenty-four hours after incubation, cell viability, cell death pathways, reactive oxygen species (ROS), inflammatory factor gene expression, and insulin secretion were evaluated. Results: SA dose-dependently decreased cell viability, increased apoptosis, ROS generation, expression of inflammatory mediators (NF-kappa B, IL-1 beta, and TNF-alpha), and insulin secretion. AZA was able to ameliorate all these changes significantly. Conclusion: Our results indicate that SA can potentially disrupt cellular homeostasis and function in the islets of Langerhans and can increase the risk of metabolic diseases such as diabetes. On the other hand, AZA protected islets of Langerhans against the toxic effects of SA, seemingly due to its antiapoptotic, anti-inflammatory, and anti-oxidant properties, indicating that AZA may have the potential to run intracellular mechanisms beneficial for coping with the metabolic toxicity of arsenic.