Recently, Lean Six Sigma (LSS) has attracted much attention from both researchers and practitioners. In fact, many published papers used a quantitative research methodology to build and test theory in the field of LSS implementation in manufacturing area. Very few studies have been reported about the critical success factors influencing of six sigma implementations. The aim of this study is to present the results, from an empirical evidence, of Six Sigma implementation in Tunisian manufacturing. Therefore, fourteen main factors have been identified through literature review and questionnaire survey. Interpretive structural modeling (ISM) has been used to develop a hierarchical structure for analyzing the interactions among the key factors. By using the MICMAC technique, the barriers were classified into four groups according to their driving power and dependence power. Our finding provides important insight to managers and practitioners about factors in the LSS implementation process.