The micro-particles in oil and gas reservoir sand can block the metal mesh used to stop sand particles entering the product stream, which will cause the production to decrease or shutdown. In order to help resolve these problems, this paper studied the mechanisms of micro-particles plugging metal mesh. The plugging mechanisms of metal mesh screen caused by different micro-particles compositions at different sand production sequences were put forward. The oil and gas well sand control simulation experimental device was used to study the plugging process, plugging mechanisms and effects of the metal mesh screen on the sand control process by micro-particles. The factors affecting the degree of plugging of the metal mesh screen was also studied here. The results show that: (1) The metal mesh screen plugging is very sensitive to the montmorillonite content of the micro-particles. The higher the montmorillonite content, the more rapidly the production capacity decreased. The boundary of the serious blockage of montmorillonite contents is 10%.  (2) The more components of the micro-particles, the faster the metal mesh screen was blocked, and the blockage was more serious. When the micro-particles are a single group, the oil well production index of the blocked screen pipe with pure montmorillonite is minimum. (3) The mud cake outside the screen is apparently layered. It shows that the hydration swelling characteristics of clay and the formation of the mud cake are two important factors that cause the pore throat blockage of the metal mesh screen.