The loss of cell function in Type 1 and Type 2 diabetes leads to metabolic dysregulation and an inability to maintain normoglycemia. The noninvasive imaging of cell function in vivo would therefore provide a valuable diagnostic and research tool for quantifying progression to diabetes and response to therapeutic intervention. Because manganese (Mn) is a T1-shortening magnetic resonance imaging (MRI) contrast agent that enters cells such as pancreatic cells through voltage-gated calcium channels, we hypothesized that Mn-enhanced MRI of the pancreas following glucose infusion would allow for non-invasive detection of cell function in vivo. To test this hypothesis, we administered glucose and saline challenges intravenously to normal mice and to mice given high or low doses of streptozotocin (STZ) to induce diabetes. Serial inversion recovery MRI was subsequently performed after Mn injection to probe Mn accumulation in the pancreas. Time intensity curves of the pancreas (normalized to the liver) fit to a sigmoid function showed a 51% increase in signal plateau height after glucose stimulation relative to saline (p < 0.01) in normal mice. In diabetic mice given a high dose of STZ, only a 9% increase in plateau signal intensity was observed after glucose challenge (p = ns); in mice given a low dose of STZ, a 20% increase in plateau signal intensity was seen after glucose challenge (p = 0.02). Consistent with these imaging findings, the pancreatic insulin content of high and low dose STZ diabetic mice was reduced about 20-fold and 10-fold, respectively, compared to normal mice. We conclude that Mn-enhanced MRI demonstrates excellent potential as a means for noninvasively monitoring cell function in vivo and may have the sensitivity to detect progressive decreases in function that occur in the diabetic disease process.