Psammomys obesus, a desert rodent, develops diabetes when displaced from its natural environment and fed a high energy diet in the laboratory. This study was designed to examine variations in renal function in relation to the diabetic state with emphasis on changes in Na-K-ATPase activity. The following groups of Psammomys were studied: (1) Animals fed a saltbush diet; a low energy/high salt diet (natural). (2) Animals fed a low energy/low salt diet (laboratory). Both 1 and 2 were normoglycemic and normoinsulinemic and thus served as control. (3) Animals fed a high energy diet (group C) who were hyperglycemic and hyperinsulinemic; this group was divided into two subgroups: C1 presented with glomerular hyperfiltration rate and C2 with glomerular hypofiltration rate. (4) Animals fed a high energy diet presenting with hyperglycemia-hypoinsulinemia (group D). (5) Group D+I, similar to group D but treated with external insulin (2 U/24 h). Groups D and C1, whose glomerular filtration rose above normal by 30% and 70% respectively, exhibited metabolic similarity to Type I and Type II diabetes. In these groups, Na-K-ATPase activity in the cortex increased by 80-100% and in the medulla by 180% (P<0.001 vs control). In group C2 with reduced glomerular filtration rate (GFR), Na-K-ATPase activity did not differ from control. In group D+I, with normalized glomerular filtration rate, Na-K-ATPase activity was similar to control. There was a linear and significant correlation between GFR and Na-K-ATPase activity both in the cortex and in the medulla. These experiments present a well defined animal model of diabetes mellitus. Variations in glucose and in insulin did not correlate with Na-K-ATPase activity. These results clearly demonstrated that Na-K-ATPase activity in the diabetic Psammomys was determined by glomerular filtration but was independent of plasma glucose or insulin levels.