Paliperidone prolongs cardiac repolarization in a concentration-dependent manner. Meanwhile, continuous infusion of intravenous lipid emulsion (ILE) has been established as a detoxification therapy for lipophilic drugs. However, this change in pharmacokinetics of various drugs following ILE administration remains to be clarified. Our objective is to clarify the effect of continuous infusion of ILE on the pharmacokinetics of overdosed paliperidone in rats. Paliperidone (20 mg/kg) was administered orally to free-moving male Wistar rats. Continuous infusion (initial loading dose: 4 ml/kg for 10 min, followed by 4 ml/kg/h for 12 h) of ILE or acetated Ringer's solution (AR) was initiated 30 min after paliperidone administration. Plasma concentration profile of paliperidone was monitored for 12 h after administration. The plasma concentration and tissue/plasma concentration ratios of paliperidone were compared between ILE and AR groups. The rat group infused with ILE showed a higher area under the concentration–time curve (mean [S.D.]: 6102 [900.9] vs. 3407 [992.1] ng h ml−1, p = 0.02) and longer elimination half-time (t1/2) (4.1 [0.9] vs. 2.2 [0.4] h, p = 0.02) compared with the AR group. Tissue/plasma concentration ratios of paliperidone were lower in ILE rats than in AR rats (1.98 [0.70] vs. 3.82 [1.47] in the heart, p = 0.04; 0.28 [0.29] vs. 1.27 [0.58] in the brain, p < 0.001). In conclusion, continuous infusion of ILE would reduce tissue distribution and prolonged the t1/2 of paliperidone in rats. These results suggest that continuous infusion of ILE has potential as an emergency treatment for acute paliperidone intoxication.