The purpose of the present study was to prepare multivesicular liposomes (MVL) with a high drug loading capacity for intramuscular sustained release and to investigate their potential applicability towards tramadol, and to improve the stability of liposomes by coating PEG. The basic physiochemical properties of tramadol MVLs and PEG-coated MVLs were studied. The average particle sizes of optimum preparation were 18.2 microm and 31.3 microm. The entrapment efficiency was up to 80%. The encapsulation efficiency of tramadol MVLs and PEG-coated MVLs was measured. The results confirmed the possibility of multivesicular liposomes as a sustained-release delivery system. Tramadol was continuously released from MVL formulations in PBS (pH 6.8) in vitro, and reached a maximum of 80% within 72 h. The results show that tramadol PEG-coated MVLs could provide sustained release according to the first order kinetic equation.