The present study aimed to analyze the impact of tartrazine (T) and crocin (Cr) applications on the pancreas tissues of the Wistar rats. A total of 40 Wistar rats were randomly divided into 4 groups with 10 rats in each group, including the Control, T, Cr, and T + Cr groups. After 3 weeks of application, the pancreatic tissues of the rats were removed under anesthesia and rat blood samples were obtained. Tissues were analyzed with biochemical and histopathological methods. It was determined that T administration increased malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), glucose, triglyceride, LDL, VLDL, and total cholesterol levels. However, it decreased reduced glutathione (GSH), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT), and HDL levels when compared with the other groups. It was observed that Cr administration significantly increased GSH, SOD, CAT, TAS, and HDL levels when compared with the control group. In the T group, histopathological changes were observed in pancreatic tissue, leading to damages in exocrine pancreas and islets of Langerhans and increased caspase-3 immunoreactivity (p <= 0.001). Co-administration of Cr and T brought the biochemical and histopathological findings closer to the control group levels. The administration of T induced damage in the pancreas with the administered dose and frequency. Cr can increase the antioxidant capacity in pancreas tissue. Co-administration of T and Cr contributed to the reduction of the toxic effects induced by T. It could be suggested that Cr administration ameliorated T toxicity.