To evaluate glomerular filtration rate (GFR) estimation by means of plasma clearance of iohexol (IOX) in domestic rabbits and to assess accuracy of limited-sampling models for GFR estimation. 6 healthy domestic rabbits (Oryctolagus cuniculus). Each rabbit received IOX (64.7 mg/kg [0.1 mL/kg], IV), and blood samples were collected at predetermined times before and after administration. Plasma IOX concentration was determined by high-performance liquid chromatography. The pharmacokinetics of IOX was determined by a noncompartmental method. For each rabbit, plasma clearance of IOX was determined by dividing the total IOX dose administered by the area under the concentration-time curve indexed to the subject's body weight. The GFR estimated from the plasma IOX concentration at 6 sampling times (referent model) was compared with that estimated from the plasma IOX concentration at 5 (model A), 4 (model B), and 3 (models C, D, and E) sampling times (limited-sampling models). Mean ± SD GFR was 4.41 ± 1.10 mL/min/kg for the referent model and did not differ significantly from the GFR estimated by any of the limited-sampling models. The GFR bias magnitude relative to the referent model was smallest for model D in which GFR was estimated from plasma IOX concentrations at 5, 15, and 90 minutes after IOX administration. Results suggested that plasma clearance of IOX was a safe, reliable, accurate, and clinically feasible method to estimate GFR in domestic rabbits. Further research is necessary to refine the method.