This work concerns the design and the optimization of reconfigurable transfer lines. The principle objective is to design a machining line with less cost while respecting the technological and economic constraints of the problem. The corresponding optimization problem is a transfer lines balancing problem subject to specific constraints. It consists to affect operations to workstations minimizing the installations cost. In addition to the habitual constraints of the transfer balancing problem, i.e. precedence, inclusion and exclusion constraints, we consider accessibility constraints. In addition, the principal specificity of reconfigurable lines compared to the dedicated transfer lines, comes from the sequential execution of operations. This often makes it necessary to set up stations with several machining centers working in parallel to achieve desired production volumes. Finally, the utilization of mono-spindle head machining center induces the inclusion of setup times between operations. This setup time is due to the time of displacement and change of tools which it depends of the operational sequence. We proposed firstly a mathematical formalization of the problem using a mixed integer program. We developed also several methods to calculate lower bounds and a pretreatment procedure. However, the additional constraints make the resolution of the considered balancing problem very difficult and the proposed approach generally does not solve instances of industrial size. To meet this need, we have developed several approximate resolution methods of the problem taking inspiration from effective Metaheuristics on combinatorial optimization problems.