The purpose of this study was to investigate the mechanisms of insulin resist.ance on receptor and post- receptor phases in streptozotocin (STZ)-induced diabetic rats. Rats were randamly assigned to contsol, mild, and sever.. Diabetic rats. I)iabetes was induced by intraper- itoneal administration of 35(mild diabetes) or 45 mg/kg BW/day (severe diabetes) STZ on 2 consequtive days. The experiement was carried out following overnight fasting, 5 weeks after the STZ-administration. The experiment yielded the fo11owing resuIts. Plasma insulin level was decreased in the diabetic rats compared with control ones, with the level decreasing with the severity of diabetes (control, mild and severe diabetes, 42+-6,9, 28+-4.7 and 14+-3.3 Pu/ml, respectively). Plasrna glucose level was markedly increased in the diabetic rats compared with control ones, with the Ievel increasing with the severity of diabetes (control, mild and severe diabetes, 93+-12, 137+32 and 347+-42 mg/dl, respectively). Insulin binding to the crude p1asma membrane from hindlimb muscles and liver were increased as the severity of diabetes increased compared with control rats These results were thought to be caused by up-regulation of the receptor concentration(Ro) in response to decrease of insulin secretion although decrease of the msuJin binding affinity(Ke) in diabetic rats by the Srat chard plot analysis (Ro (fmol /100 pg protein) of control, mild and severe diabetes, 24,6, 36. 4 and 45.3 in muscle, and 64.8, 93.5 and 107.6 in liver, respectiively; ke(10' mol) of control, mild and severe diabetes, 3.32, 2.89 and 2.96 in muscle, and 3.63, 2.94 and 3.48 m liver. Respectively). D-glucose-inhibitable cytochalasin B binding to plasrna and intracellular membranes from hindlimb musc:les were decreased as thc severity of diabetes increased compared with control .,its It was thought to be caused by decrease of the cytochalasin B binding sites (Ro) by Scatchard plot analysis (Ro (pmol!mg proteinj of control, mild and severe rliabetes, 10.2, 7.0 and 6.0 in plasma membrane, and 13.9, 9., and 7,8 in intracellular membranes, respectively) Above results suggest in STZ-induced diabetic rats that the insulin resistance an the receptor phase due to deerease of binding affinity in hindlamb muscles and liver is likeJy to exist, and that this may be due to structural changes of receptor, and that insulin resistance on the post-receptor phase due to decrease of the number of glucose transporter exist, and that the degree of insulin resistance is increased in proportioin to the severity of diabetes.