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A CMOS bio-inspired motion direction sensor structure and its associated computation method are proposed. Both method and structure with excitation-inhibition operation are derived from the directionally selective ganglion cells (DSGCs) in the retina to mimic their functions. Edge-number normalization for direction calculation and pseudo-random tessellation (PRT) structure for pixel layout arrangement are also proposed to enhance the accuracy of the computation. An experimental chip based on the proposed method and structure has been designed, fabricated, and measured. The chip comprised 32 × 32 pixels with a pixel size of 63 × 63 μm2 and a fill factor of 12.8%. The total chip size is 3.3 × 4.2 mm2 and the power consumption is 9.9 mW in the dark and 21 mW at a maximum clock rate of 10 MHz with 3.3-V power supply. The fabricated chip has been measured with different moving patterns, and a computation error of less than 11 degrees has been accomplished. This verifies the correct functions of the proposed motion direction sensor. With the capability of real-time motion detection and processing under low power dissipation, the proposed sensor is feasible for many applications.