Two plasma insulin estimators are derived and evaluated in this paper. The estimators use continuously monitored plasma glucose, and they are based on a simple mathematical model of glucose-insulin metabolism. The first estimator (Estimator 1) was obtained from the glucose subsystem of the simplified model, which includes plasma glucose and interstitial insulin compartments. The second estimator (Estimator 2) was developed from the insulin kinetics subsystem of the simplified model. The performances of the estimators were compared using computer simulations and data from clinical intravenous glucose tolerance test procedures and from animal experiments.