AbstractIn this paper, we report the evolution (generation, amplification, and dissipation) of optically observed mesoscale field‐aligned irregularity structures (FAIs) (~150 km) associated with a medium‐scale traveling ionospheric disturbance (MSTID) event. There have not been observations of mesoscale FAIs of airglow before. The mesoscale FAIs were generated in an airglow‐depleted front of southwestward propagating MSTIDs that were simultaneously observed by an all‐sky imager, a GPS monitor, and a digisonde around Xinglong (40.4°N, 30.5° magnetic latitude), China, on 17/18 February 2012. A normalized cross‐correlation method has been used to obtain the velocities of mesoscale FAIs and MSTIDs. The mesoscale FAIs had an obvious northwestward relative velocity to main‐body MSTIDs (about 87.0 m/s on average). The direction of this relative velocity was roughly parallel to the depleted fronts. Furthermore, the evolution of the mesoscale FAIs was mostly controlled by the intensity of the depleted fronts. Occurred in a highly elevated ionosphere that had a total electron content depletion associated with large negative airglow perturbations (−25%), the mesoscale FAIs grew rapidly when they experienced southeastward wind, which had a speed of about 100 m/s and were measured by a Fabry‐Perot interferometer. A northeastward polarization electric field within a depleted airglow front can play a controlling role in the development of the mesoscale FAIs. The electric field can significantly elevate the ionosphere and move the mesoscale FAIs northwestward by the E × B drift. The processes for the generation and development of the polarization electric field and the mesoscale FAIs, however, need further study.