Pregnancy is associated with a depression of the immune inflammatory system, and with increased growth and function of the pancreatic islets of Langerhans. We monitored glucosuria, blood glucose concentration, and lymphocytic infiltration of pancreatic islets in 30 female, 10-wk-old, pre-diabetic nonobese diabetic (NOD) mice divided into 3 treatment groups for 13 wk: group 1, saline; group 2, pregnancy hormones (dexamethasone 4 mg/Kg/day, progesterone 1.7 mg/Kg/day, growth hormone 0.6 mg/Kg/day, prolactin 1 mg/Kg/day, and estradiol 0.05 mg/Kg); and group 3, prolactin alone (1 mg/Kg/day). At sacrifice, the pancreases were fixed in paraformaldehyde and islet infiltration was evaluated. In the saline-treated group (#1) 4/10 mice developed diabetes, while in the hormone treated group (#2) none of the mice developed diabetes. Only 1/10 mice in the prolactin-treated group (#3) developed diabetes during the study. Islets from the hormone cocktail treated group were significantly less infiltrated than islets from the other 2 treatment groups (p <0.001). Thus, the pregnancy hormones protected NOD mice from developing diabetes and significantly reduced or eliminated insulitis and islet infiltration. Prolactin alone had a partial protective effect. The results have implications for prevention of type 1 diabetes and for immune suppression in patients receiving islet cell transplantation.