Therapies exist for acute organophosphate (OP) exposure but mortality rates remain high (10% to 20%). Currently, treatment focuses on reversing the resultant cholinergic excess effects through the use of atropine. Intralipid fat emulsion (IFE) has been used to treat lipophilic drug ingestions and theoretically would be beneficial for some OP agents. The hypothesis was that IFE would decrease the acute respiratory depressant effects following lethal OP exposure using a lipophilic OP agent (parathion). The authors used a previously validated animal model of OP poisoning with detailed physiologic respiratory recordings. The model consisted of Wistar rats anesthetized but spontaneously breathing 100% oxygen. Airflow, respiratory rate, tidal volume, mean arterial pressure, and pulse rate were digitally recorded for 120 minutes following OP exposure or until respiratory failure. Three study groups included parathion alone (n = 6), parathion and IFE 5 minutes after poisoning (n = 6), and parathion and IFE 20 minutes after poisoning (n = 6). In all groups, parathion was given as a single oral dose of 54 mg/kg (four times the rat oral 50% population lethal dose [LD(50) ]). Three boluses of IFE (15 mg/kg/min) were given over 3 minutes, 20 minutes apart, starting either 5 or 20 minutes after poisoning. Timing of IFE was based on parathion kinetics. In one study group IFE was initiated 5 minutes after poisoning to coincide with initial absorption of parathion. In another study group IFE was given at 20 minutes to coincide with peak intravenous (IV) parathion concentration. Primary outcome was percentage of animals with apnea. Secondary outcome was time to apnea. Animals exposed to parathion alone demonstrated a steady decline in respiratory rate and tidal volume postexposure, with apnea occurring a mean of 51.6 minutes after poisoning (95% confidence interval [CI] = 35.8 to 53.2 minutes). Animals treated with IFE 5 minutes postexposure demonstrated no difference in mean time to apnea (44.5 minutes vs. 51.6 minutes, p = 0.29) or number of animals with respiratory arrest (100% vs. 100%, p = 1.00). Animals treated with IFE 20 minutes postexposure demonstrated a significantly prolonged mean time to apnea (95.3 minutes vs. 51.6 minutes, p = 0.002), but there was no difference in number of animals with respiratory arrest (100% vs. 66.7%, p = 0.45). All animals exposed to 4 × LD(50) of oral parathion demonstrate apnea and respiratory arrest. IFE given immediately after oral parathion does not prolong time to apnea. IFE given 20 minutes after oral exposure to parathion decreases the acute effects of the OP and prolongs the time to apnea.