We assessed the effect of a lipid emulsion of bupivacaine on prolonging peripheral nerve and epidural anesthetic blockade in the rat. The intensity and duration of motor and sensory blockade produced by a single injection of aqueous solution (BPV-as) and lipid emulsion (BPV-em) preparations of 0.5% bupivacaine were evaluated by electrophysiological methods. Both preparations induced complete, reversible motor and sensory blockade after injection. The latency time to the maximal blockade and the duration of anesthetic blockade were more prolonged for BPV-em than for BPV-as. The increase in duration of maximal blockade was 1.4 times for nerve and 1.3 times for epidural anesthesia. Histological evaluation of spinal roots and spinal cord sections did not show any abnormalities or differences between animals injected with BPV-as and those injected with BPV-em. Pharmacokinetic studies showed lower plasma peak concentration and a longer elimination half-life for BPV-em than for BPV-as. Thus, BPV-em prolongs the effects of local anesthetics, allows a similar degree of blockade, and reduces the systems toxic effects of anesthetics compared with BPV-as. Implications: We assessed a lipid emulsion containing bupivacaine for peripheral nerve and epidural anesthetic blockade in the rat. The emulsion allowed a complete blockade, while increasing the duration of the anesthetic effect (by 30%-40%), compared with the standard bupivacaine aqueous solution.