Patchy cleaning is one of issues often encountered for pleated filter cartridges (in an industrial filtration system) undergoing the reverse flow cleaning for filtration medium regeneration. To improve the cleaning quality for pleated filter cartridges, a novel reverse multi-pulsing jet cleaning was introduced in this study. A CFD modeling, via ANSYS CFX R.14, was applied to study the time-dependent flow and pressure fields in a simple filtration system with one filter cartridge under the proposed reverse flow cleaning. The transient static pressure fields for pleated cartridges under the cleaning with four flow pulsing waveforms and three pulsing frequencies were investigated. Cartridges with triangular pleats were selected as the model cartridge. It was found that the reverse multi-pulsing jet operation was able to effectively improve the cleaning performance without the increase of compressed gas tank pressure. The studied operation increased the number of cleaning action and local acceleration at the top sections of filter cartridges. In addition, the surface-averaged peak pressure drop across pleated filter media at the base section of cartridges was also 6.5% increased when pleated cartridges were cleaned by the proposed scheme as compared to that cleaned by the single-pulsing flow scheme. The peak pressure drop increase enhanced the cleaning mechanical stress at the base section of cartridges. The better performance for reverse flow cleaning was found in the multi-pulsing mode having the rectangular waveform and at high frequency. The observed peak pressure drop increase at the base section of filters was found closely related to the interaction of residual gas from the former pulsing and jet flow from the later pulsing. Further investigation indicated that the observed cleaning performance improvement was also shown under the consideration of the tank pressure reduction and change of media permeability during the removal of dust cake built-up on filter surface.