The high-cycle fatigue mechanisms of a NiTi shape memory alloy (SMA) under three different mean strains were investigated. Cold-rolled NiTi SMA specimens were heat treated at 600°C for 30min was selected to perform the fatigue test. Three samples were conducted cyclic deformation up to 2×105 cycles with three mean strains that subjected at full austenite, total stress-induced martensite (SIM) and austenite-martensite coexist status with the same strain amplitude of 0.25%. The cyclic stress-strain (CSS) curves show different cyclic softening and hardening at different mean strains. The S-S curves also reveal that cyclic deformation strain mainly occurred in martensite phase although austenite and martensite (A-M) coexisted. The transmission electron microscopy (TEM) investigation shows that slip dislocations with habit plane and basal plane dislocations were induced during the cycling, and these microstructure evolutions contribute to the cyclic softening and hardening.