Highly inbred Lewis rats with streptozotocin-induced diabetes mellitus of 7 mo duration received intraportal transplants of neonatal pancreatic tissue. At 7 and 9 mo of diabetes (at the time of and at 2 mo after islet transplantation) renal biopsies for the evaluation of several morphometric parameters were obtained from control (C), diabetic-nontransplanted (D), and diabetic-transplanted (D-T: with normal plasma glucose values) rats. Glomerular volume in D-T animals at 9 mo fell to a value less than that in C rats while glomerular volume in D animals exceeded that in C rats at both 7 and 9 mo. Electron microscopic morphometry of the total mesangium and its cellular and matrix components documented a nearly twofold increase in the volume of the mesangial matrix in D as compared with C rats at both 7 and 9 mo. While the mesangial cellular component was also increased in diabetes, the changes in the volume of the mesangial matrix in D rats at both 7 and 9 mo provided tha major proportion of the increased volume of the total mesangium. With islet transplantation, significant reduction in the volumes of the mesangial matrix and a much smaller and not significant decrease in the cellular component gave normal values for those components and for the volume of the total mesangium in D-T animals. The expanded volume of the total mesangium in diabetes concomitantly increased the proportion of the glomerular capillary surface interfaced with the mesangium. Similarly, the proportion of the glomerular basement membrane (GBM)-epithelium interface juxtaposed to the mesangium was elevated in diabetes. These two observations imply that the expanding mesangium interposed itself between the endothelial cells and the GBM, increasing the surface of the mesangium. With islet transplantation these surface alterations returned toward normal in conjunction with the reduction in volume of the mesangium. These observations with electron microscopic morphometry provide detailed documentation of the alterations in the mesangium of experimental diabetes mellitus. The sensitivity with which these changes can be monitored permit detailed analysis of subtle increases in both mesangial surface and volume in diabetes mellitus.