In order to explore the physiological characteristics and the transcriptional regulation of OsDSR2 RNAi transgenic rice under salt stress, we analyzed the physiological indicators and the transcriptome profiles of OsDSR2 RNAi transgenic rice seedlings compared to wild type Zhonghua 11(ZH11) plants. Analysis of the various physiological indexes under normal conditions revealed no significant difference in OsDSR2 RNAi transgenic line and ZH11. Under salt stress treatments, no significant difference on the content of chlorophyll, soluble sugar (SS), superoxide dismutase (SOD) activity and catalase (CAT) activity of OsDSR2 RNAi transgenic rice to ZH11 was detected, while the content of cell membrane permeability, malondialdehyde (MDA) and Na+/K + in transgenic rice were detected to be significantly lower; the content of Proline (Pro) and peroxidase (POD) activity were significantly higher than those of ZH11. The transcriptome analysis revealed 68 differentially expressed genes in OsDSR2 RNAi transgenic plants before and after salt stress treatment, 55 genes of which were up-regulated and 13 genes of which were down-regulated. GO analysis showed that the differentially expressed genes were enriched in stress response, catabolism and other biological processes. KEGG analysis showed that the differentially expressed genes were mainly involved in the biosynthesis of carotenoids, brassinolactone and the biosynthesis of epidermal, cork and wax biosynthesis pathways. The differential expression of OsbZIP16, OsLEA3, RAB21 and other stress-related genes under treatments was further verified by RT-qPCR. Taken together, the OsDSR2 RNAi transgenic rice plants showed the salt tolerance which might be associated with the reduction of the cell membrane permeability, the content of MDA and Na+/K +, the Pro and POD activities as well as the inhibition of the chlorophyll degradation. Furthermore, OsDSR2 gene might be also involved in the transcriptional regulation of OsLEA3, RAB21, OsbZIP16 and plant cuticular wax biosynthesis gene (LOC_Os04g28620).