Rice blast disease caused by the filamentous Ascomycetous fungus Magnaporthe oryzae is a major threat to rice production worldwide. The mechanisms underlying rice resistance to M. oryzae, such as transcriptional reprogramming and signalling networks, remain elusive. In this study, we carried out an in-depth comparative transcriptome study on the susceptible and resistant rice cultivars in response to M. oryzae. Our analysis highlighted that rapid, high-amplitude transcriptional reprogramming was important for rice defence against blast fungus. Ribosome- and protein translation-related genes were significantly enriched among differentially expressed genes (DEGs) at 12 hpi in both cultivars, indicating that the protein translation machinery is regulated in the activation of immunity in rice. Furthermore, we identified a core set of genes that are involved in the rice response to both biotic and abiotic stress. More importantly, among the core genes, we demonstrated that the metallothionein OsMT1a and OsMT1b genes positively regulated rice resistance while a peroxidase gene Perox4 negatively regulated rice resistance to M. oryzae. Our study provides novel insight into transcriptional reprogramming and serves as a valuable resource for functional studies on rice immune signalling components in resistance to blast disease.