During the process of islet isolation, pancreatic enzymes are activated and released, adversely affecting islet survival and function. We hypothesize that the exocrine component of pancreases harvested from pre-weaned juvenile pigs is immature and hence pancreatic tissue from these donors is protected from injury during isolation and prolonged tissue culture.Biopsy specimens taken from pancreases harvested from neonatal (5-10 days), pre-weaned juvenile (18-22 days), weaned juvenile (45-60 days), and young adult pigs (>90 days) were fixed and stained with hematoxylin and eosin. Sections were examined under a fluorescent microscope to evaluate exocrine zymogen fluorescence intensity (ZFI) and under an electron microscope to evaluate exocrine zymogen granule density (ZGD).Exocrine content estimation showed significantly lower ZFI and ZGD in juvenile pig pancreases (1.5 ± 0.04 U/μm(2) , ZFI; 1.03 ± 0.07 × 10(3) /100 μm(2) , ZGD) compared to young adult pigs (2.4 ± 0.05U/μm(2) , ZFI; 1.53 ± 0.08 × 10(3) /100 μm(2) ZGD). Islets in juvenile pig pancreases were on average smaller (105.2 ± 11.2 μm) than islets in young adult pigs (192 ± 7.7 μm), but their insulin content was comparable (80.9 ± 2.2% juvenile; 84.2 ± 0.3% young adult, P > 0.05). All data expressed as mean ± SEM.Porcine islet xenotransplantation continues to make strides toward utilization in clinical trials of type 1 diabetes. Porcine donor age and weaning status influence the extent of exocrine maturation of the pancreas. Juvenile porcine pancreases may represent an alternative donor source for islet xenotransplantation as their exocrine component is relatively immature; this preserves islet viability during extended tissue culture following isolation.