The manufacturing enterprises above designated siz are the main components of industrial enterprises, and the manufacturing enterprises above designated size are the main body of social innovation. So we need to understand the R&D input-output efficiency for the manufacturing enterprises above designated size, and find an effective way to improve its efficiency. The DEA model was used to quantitatively evaluate the R&D input-output efficiency in 31 industries and 16 regions in Anhui Province. The study analysis found, R&D input-output efficiency is higher for most manufacturing enterprises above designated size in Anhui Province, but there are still phenomenon of R&D inputs wasteful and R&D output shortage in some industries. In addition, there are unbalanced R&D resource allocation in different regions of Anhui Province. Therefore, we must strengthen the government policy guidance, establish and develop the industrial clusters, play a regional advantage, and in order to optimize the R&D resource allocation, narrow the gap between industries and regions.