The hypoglycemic effect of the rhizomes of Smilax glabra ROXBURGH (Liliaceae) was investigated in normal and KK-Ay mice, one of the animal models of non-insulin dependent diabetes mellitus (NIDDM) with hyperinsulinemia. The methanol extract of rhizomes of Smilax glabra ROXBURGH (SM, 100 mg/kg body weight) reduced the blood glucose of normal mice 4 h after intraperitoneal administration (p<0.05), and also significantly lowered the blood glucose of KK-Ay mice under similar conditions (p<0.001). However, SM did not affect the blood glucose in streptozotocin-induced diabetic mice, one of the animal models of insulin-dependent diabetes mellitus (IDDM) with hypoinsulinemia. SM also suppressed epinephrine-induced hyperglycemia in mice. SM-treated KK-Ay mice significantly decreased the blood glucose in an insulin tolerance test. We concluded that the hypoglycemic effect of SM raised insulin sensitivity.