The objectives of this study were to evaluate the safety and tolerability of RheothRx (poloxamer 188) Injection administered as an intravenous (iv) infusion to healthy male volunteers and to determine the pharmacokinetic profile of poloxamer 188. Thirty‐six healthy male volunteers were enrolled in a randomized, double‐blind, placebo‐controlled, dose‐escalation trial for RheothRx Injection. The volunteers were randomized to three treatment groups (12 per treatment group, with eight receiving active therapy and four receiving placebo). In each treatment group, volunteers received RheothRx Injection or placebo as an iv infusion on two occasions at least 3 weeks apart to make a total of six doses being studied (10, 30, and 45 mg/kg/h for 72 h, 60 mg/kg/h for 43.3 to 72 h, 60 and 90 mg/kg/h for 24 h). Serial plasma samples were collected during and up to 36 h after the end of the infusions; urine was collected over intervals from the start of the infusion until 36 h after the infusions were terminated. Plasma and urine samples were assayed for poloxamer 188 by gel‐permeation chromatography. Pharmacokinetic parameter values were calculated by noncompartmental and compartmental methods. Poloxamer 188 was eliminated primarily by renal excretion. Estimates of clearance, elimination rate constant, and apparent volume of distribution at steady state values were independent of infusion rate. Poloxamer 188 displayed no apparent infusion rate dependence in its pharmacoki‐netics.