Two steps are involved to determine transmission ratios of serial robot, i.e. relative proportion of transmission ratios determination and absolute transmission ratios determination, and the former is stressed from viewpoint of manipulability. Based on analyzing the essence of manipulability index related with condition number, the determination of relative proportion of transmission ratios was formulated as optimization of manipulability related to driving space. An optimization model on the basis of global manipulability related to driving space was given to determinate relative proportion of transmission ratios. A method to obtain Jacobi matrix in the optimization model was proposed with consideration of the difference of power elements’ velocity driving capability and endeffecter’ pose velocity of job requirement. At last, an optimization process was conducted to determine relative proportion of transmission ratios of a 6-DOF serial robot, and its global manipulability related to driving space was increased.