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The performance of a completely implantable peritoneal artificial pancreas (AP) has been demonstrated in principle in a live diabetic domestic pig. The device consists of a smart glucose-sensitive gel that forms a gateway to an insulin reservoir and is designed to both sense glucose and deliver insulin in the peritoneal cavity. It can be refilled with insulin via subcutaneous ports and surgery was developed to insert the AP. Diabetes was induced with streptozotocin (STZ), the device filled with insulin (Humulin® R U-500) in situ and the animal observed for several weeks, during which time there was normal access to food and water and several oral glucose challenges. Blood glucose (BG) levels were brought down from >30 mmol/L (540 mg/dL) to non-fasted values between 7 and 13 mmol/L (126–234 mg/dL) about five days after filling the device. Glucose challenge responses improved ultimately so that, starting at 10 mmol/L (180 mg/dL), the BG peak was 18 mmol/L (324 mg/dL) and fell to 7 mmol/L (126 mg/dL) after 30 min, contrasting with intravenous attempts. The reservoir solution was removed after 8 days of blood glucose levels during which they had been increasingly better controlled. A rapid return to diabetic BG levels (30 mmol/L) occurred only after a further 24 days implying some insulin had remained in the device after removal of the reservoir solution. Thus, the closed loop system appeared to have particular influence on the basal and bolus needs for the 8 days in which the reservoir solution was in place and substantial impact for a further 3 weeks. No additional insulin manual adjustment was given during this period.