As compared to centralized servers, cross-regional clustering message have advantages in terms of low cost, high fault tolerance, easy expansion and load balance so that clustering message severs become one of the major directions to solve the middleware server performance problems and improve cross-regional service capabilities. Based on the deep analysis of the working principle and operation mechanism of message-oriented middleware, this article proposes a cross-regional clustering technology of message-oriented middleware, which focuses on solving the technical difficulties of nodes synchronization, multi-active service and load balance in cross-regional cluster. Experiments show that the solution works well.