Non-Blocking Multithreaded architectures have been proposed as an effective means to overlap computation and communication in distributed memory systems. However, in these models, communication latency could only be hidden from computation as long as there are enough ready threads. In this paper, we describe our I-Structure Software Cache (ISSC) runtime system, which takes advantage of the global data locality in these models without adding any specific hardware support. Our ISSC provides a communication latency reduction technique in non-blocking multithreaded architectures while maintaining the ability of tolerating communication latency. Our simulation results show that our ISSC runtime system dramatically decreases network traffic by caching remote requests and also achieves 70% to 95% improvement on the system performance(speedup).