Bubble defect is a major problem in R2R UV imprinting of micro pyramid arrays. It renders the structure incomplete and significantly downgrades the optical performance of its light reflection ability. This study aims to investigate the influence of processing parameters on the generation of bubble defects in micro pyramid arrays fabricated by R2R UV imprinting, and eliminate the existence of bubbles in the fabricated structures. Box-Behnken method (BBD) was used to design the experiments. Three processing parameters, mold temperature, pressure, web speed, were selected and their impact on the generation of bubble defects in micro pyramid arrays was studied. The experiment results were investigated and a method was proposed to grade the seriousness of bubble defects in the fabricated structures. It was found from the study that the processing parameters play important roles in affecting the bubble defect generation in the micro pyramid arrays, and manufacturing of micro pyramid arrays almost free of bubble defects using R2R UV imprinting technique is possible through the selection of right combination of processing parameters.