We compared the efficacy of articaine encapsulated in multilamellar and unilamellar liposomes with that of articaine with epinephrine, after infiltration into inflamed and uninflamed tissue in rats. We encapsulated 4% articaine in multilamellar (articaine:multi) and unilamellar (articaine:uni) liposomes and compared them with 4% articaine with 1:100 000 epinephrine (articaine:epinephrine), in inflamed (plantar incision into the hind paw) and uninflamed (infraorbital nerve block) tissue in rats. Anaesthetic formulations (0.1ml) were injected near the right infraorbital foramen in uninflamed tissue, where success and duration of anaesthesia were assessed by pinching the upper lip every 5minutes. For inflamed tissue the anaesthetic formulations (0.1ml) were injected laterally into a surgical wound made 24hours earlier in the plantar region of the rat's right hind paw. The degree of anaesthesia was assessed by application of forces laterally to the wound with electronic von Frey filaments. Articaine:uni resulted in less successful anaesthesia than both articaine:multi (p=1.1x10-5) and articaine:epinephrine (p=4.3x10-8) in uninflamed tissue, but there were no differences in duration or success of anaesthesia between articaine:epinephrine and articaine:multi. In inflamed tissue articaine:epinephrine gave significantly more effective anaesthesia for longer than aarticaine:uni (p=2.3x10-6), and articaine:epinephrine (p=1.8x10-6) formulations, which did not differ from each other. Multilamellar liposomal articaine could be an option for local anaesthesia in uninflamed tissues. However, articaine with epinephrine gave better results than liposomal formulations in inflamed tissue. © 2016 The British Association of Oral and Maxillofacial Surgeons.543295300