Efavirenz is a poorly water soluble drug with aqueous solubility 4 μg/mL and oral bioavailability 40-45%, having non-nucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral activity. The aim of the present study was to develop a Self-Micro-emulsifying Drug Delivery System (SMEDDS) of EFV with improved dissolution rate for the oral delivery of poorly water-soluble antiretroviral agent. The optimized SMEDDS of EFV was prepared by dissolving EFV in selected vehicles such as PEG-6 Caprylic/Capric Glycerides (Softigen® 767) as oil, Polyoxyl 35 Castor Oil (Cremophor® EL) as a surfactant and Glyceryl Caprylate/Caprate (Capmul® MCM) as co-surfactant. The proportion of oil, surfactant and co-surfactant in liquid SMEDDS of EFV was optimized using ternary phase diagram, phase separation study, droplet size analysis and in-vitro dissolution study. Optimized SMEDDS composition of oil to surfactant/co-surfactant content did not show phase separation in 0.1N HCl and water, with the droplet size varying from 39-46 nm, which indicate the formation of homogeneous stable microemulsion in both the media. In-vitro dissolution data showed surprisingly and significant enhancement of dissolution rate of EFV in form of SMEDDS compared to pure EFV powder.