Background:Obesity has been shown to trigger adaptive increases in pancreasparenchymal and fat volume. Consecutively, pancreatic steatosis may lead to beta‐cell dysfunction. However, it is not known whether the pancreatic tissue compo-nents decrease with weight loss and pancreatic steatosis is reversible followingRoux‐en‐Y gastric bypass (RYGB). Therefore, the objective of the study was toinvestigate the effects of RYGB‐induced weight loss on pancreatic volume andglucose homeostasis.Methods:Eleven patients were recruited in the Obesity Centre of the UniversityMedical Centre Hamburg‐Eppendorf. Before and 6 months after RYGB, total GLP‐1levels were measured during oral glucose tolerance test. To assess changes invisceral adipose tissue and pancreatic volume, MRI was performed. Measures ofglucose homeostasis and insulin indices were assessed. Fractional beta‐cell areawas estimated by correlation with the C‐peptide‐to‐glucose ratio; beta‐cell masswas calculated by the product of beta‐cell area and pancreas parenchymal weight.Results:Pancreas volume decreased from 83.8 (75.7‐92.0) to 70.5 (58.8‐82.3) cm3(mean [95% CI],P= .001). The decrease in total volume was associated with asignificant decrease in fat volume. Fasting insulin and C‐peptide were lower postRYGB. HOMA‐IR levels decreased, whereas insulin sensitivity increased (P= .03). Thiswas consistent with a reduction in the estimated beta‐cell area and mass.Conclusions:Following RYGB, pancreatic volume and steatosis adaptivelydecreased to“normal”levels with accompanying improvement in glucose homeosta-sis. Moreover, obesity‐driven beta‐cell expansion seems to be reversible; however,future studies must define a method to more accurately estimate functional beta‐cellmass to increase our understanding of glucose homeostasis after RYGB.