In the present work, the effect of heat treatment on the cyclic deformation behavior of as-extruded ZA81M magnesium alloy was investigated. Two heat treatment conditions were applied to the as-extruded ZA81M alloy: a solution treatment (T4, 653 K for 40 h and quenched with 298 K water) and a solution treatment plus artificial aging (T6, 348 K for 32 h (pre-aging at low temperature) and 453 K for 8 h (the second aging) and quenched with 353 K water). The results showed that the fine second phase precipitated after the aging treatment, the tensile yield strength of the T6-treated specimens increased, and the stress amplitude of T6-treated specimens was always higher than that of T4-treated specimens. The T6-treated specimens had a higher total strain energy density and a shorter fatigue life at a strain amplitude of 0.4%, and a lower total strain energy density and a longer fatigue life at a strain amplitude of 0.8%, compared to the T4-treated specimens. All fatigue cracks of the T4 and T6 ZA81M alloy were initiated at the second phase or along the grain boundary and propagated perpendicular to the loading direction.