The optimization of a primary mirror support system is one of the most critical problems in the design of large telescopes. Here, we propose a hybrid optimization methodology of variable densities mesh model (HOMVDMM) for the axial supporting design, which has three key steps: (1) creating a variable densities mesh model, which will partition the mirror into several sparse mesh areas and several dense mesh areas; (2) global optimization based on the zero-order optimization method for the support of primary mirror with a large tolerance; (3) based on the optimization results of the second step, further optimization with first-order optimization method in dense mesh areas by a small tolerance. HOMVDMM exploits the complementary merits of both the zero- and first-order optimizations, with the former in global scale and the latter in small scale. As an application, the axial support of the primary mirror of the 2.5-m wide-field survey telescope (WFST) is optimized by HOMVDMM. These three designs are obtained via a comparative study of different supporting points including 27 supporting points, 39 supporting points, and 54 supporting points. Their residual half-path length errors are 28.78, 9.32, and 5.29 nm. The latter two designs both meet the specification of WFST. In each of the three designs, a global optimization value with high accuracy will be obtained in an hour on an ordinary PC. As the results suggest, the overall performance of HOMVDMM is superior to the first-order optimization method as well as the zero-order optimization method.