Mechanical fatigue tests were conducted on specimens of A356-T6 casting alloys under multi-axial cyclic loadings with 5 loading paths (proportional, circular, square, diamond, and ellipse path). Optical microscopy and TEM were used to examine both undeformed and fatigue failure specimens. It is shown that undeformed material has coarse microstructure with low density of dislocation. Under every loading path, cyclic hardening dominates the whole fatigue process. Additional hardening is found in this casting material, but the rate and extent of cyclic hardening and additional hardening are quite dependent on particular loading paths. Various dislocation substructures are observed in the specimens including specimens fatigued to 20 cycles and fatigue failure specimens. While these dislocation substructures are determined by the moving ability of dislocation and interactions between dislocation and particles. Low cycle fatigue life is sensitive to the difference of loading paths, and the fatigue life increases as the extent of cyclic hardening decreases.