Abstract: OBJECTIVE To optimize and assess the formulation of self-microemulsifying drug delivery system mixture for felodipine. METHODS By the means of solubility, compatibility, ternary phase diagram and central composite design-response surface methodology, the preliminary formulation was settled. The self-microemulsifying efficiency, stability and dissolution were studied. RESULTS The optimized formulation was composed of LABRAFIL M 1944CS 4.4 g, Cremophor EL35 as a emulsifier 5.5 g, PEG400 1.1 g, and felodipine 1.0 g. The average particle size after the emulsification was 30.4 nm, and PDI was 0.16. The self-emulsifying efficiency and stability was excellent, and accumulative dissolution reached 85% in 5 min, and 99% in 30 min. After 24 h, the felodipine self-microemulsifying particles was still stable. CONCLUSION By the means of central composite design-response surface methodology, a felodipine self-microemulsifying mixture was obtained, which showed a high self-emusifying efficiency, stability and a good in vitro dissolution performance.