The function of OsDR8, a rice disease resistance-responsive gene, was studied. Silencing of OsDR8 using an RNA interference approach resulted in phenotypic alteration of the plants. The transgenic plants with repressed expression of OsDR8 showed reduced resistance or susceptibility to Xanthomonas oryzae pv. oryzae and Magnaporthe grisea causing bacterial blight and blast, which are two of the most devastating diseases in rice worldwide, respectively. The putative product of OsDR8 was highly homologous to an enzyme involved in the biosynthesis of the thiazole precursor of thiamine. Transgenic plants showing repressed expression of OsDR8 and reduced resistance had significantly lower levels of thiamine than the control plants. Exogenous application of thiamine could complement the compromised defense of the OsDR8-silenced plants. The expression level of several defense-responsive genes including the earlier functional genes of defense transduction pathway, OsPOX and OsPAL, and the downstream genes of the pathway, OsPR1a, OsPR1b, OsPR4, OsPR5 and OsPR10, was also decreased in the OsDR8-silenced plants. These results suggest that the impact of OsDR8 on disease resistance in rice may be through the regulation of expression of other defense-responsive genes and the site of OsDR8 function is on the upstream of the signal transduction pathway. In addition, the accumulation of thiamine may be essential for bacterial blight resistance and blast resistance.