Poorly, water soluble drugs such as cefuroxime axetil offer challenges in developing a drug product with adequate bioavailability. The main objective of present study was to prepare a lipid based self-microemulsifying drug delivery system to improve the oral bioavailability of cefuroxime axetil. The liquid self - microemulsifying drug delivery system consisted of cefuroxime axetil, Lutrol E 400, Labrasol and Gelucire 44/14. Initially liquid self - microemulsifying drug delivery system were characterized for clarity, rate of emulsification and drug loading capacity. The optimized formulation characterized for the zeta particle sizer, Differential scanning calorimetrystudies. In vitro results of self - microemulsifying drug delivery system and cefuroxime axetil were shown that the rate of drug dissolution from lipid based self-microemulsifying drug delivery system was significantly higher than commercial tablet and as well as pure drug. The results demonstrate the potential use of self - microemulsifying drug delivery system as a means of improving solubility, dissolution thereby it may enhance the bioavailability of cefuroxime axetil.