As information technology fusion is accelerated, the researches to improve the quality and productivity of crops inside a plant factory actively progress. Advanced growth environment management technology that can provide thermal environment and air flow suited to the growth of crops and considering the characteristics inside a facility is necessary to maximize productivity inside a plant factory. Currently running plant factories are designed to rely on experience or personal judgment; hence, design and operation technology specific to plant factories are not established, inherently producing problems such as uneven crop production due to the deviation of temperature and air flow and additional increases in energy consumption after prolonged cultivation. The optimization process has to be set up in advance for the arrangement of air flow devices and operation technology using computational fluid dynamics (CFD) during the design stage of a facility for plant factories to resolve the problems. In this study, the optimum arrangement and air flow of air circulation fans were investigated to save energy while minimizing temperature deviation at each point inside a plant factory using CFD. The condition for simulation was categorized into a total of 12 types according to installation location, quantity, and air flow changes in air circulation fans. Also, the variables of boundary conditions for simulation were set in the same level. The analysis results for each case showed that an average temperature of 296.33K matching with a set temperature and average air flow velocity of 0.51m/s suiting plant growth were well-maintained under Case 4 condition wherein two sets of air circulation fans were installed at the upper part of plant cultivation beds. Further, control of air circulation fan set under Case D yielded the most excellent results from Case D-3 conditions wherein air velocity at the outlet was adjusted to 2.9m/s.