Gosha-jinki-gan (GJG) is a Chinese herbal medicine that is known to be useful for the treatment of diabetic neuropathy. In the present study, the effect of GJG on insulin resistance in streptozotocin (STZ, 50 mgkg(-1) BW, i.v.) -induced diabetic rats was examined by means of the euglycemic clamp procedure. To accomplish this objective, diabetic and non-diabetic control rats were divided as follows: a single dose administration of GJG (800 mgkg(-1) BW, p.o.), saline (5 mlkg(-1) BW, p.o.), and GJG (p.o)+N(G)-monomethyl-L-arginine (L-NMMA, 1 mgkg(-1)min(-1) BW, i.v.). In diabetic rats, the incremental area (DeltaAUC [area under curve]) of the glucose metabolic clearance rate (MCR) during a 3.0 mUkg(-1)min(-1) insulin infusion rate was significantly higher in the GJG-administrated group compared to the saline-administrated one. On the other hand, the effect of GJG on the DeltaAUC of MCR in diabetic rats was abolished by L-NMMA. In addition, no significant differences in the DeltaAUC of MCR were observed in non-diabetic control rats. These results suggest that a single dose administration of GJG can improve the glucose utilization and insulin resistance in STZ-induced diabetic rats, probably via the nitric oxide (NO) pathway.