Rice sheath blight, caused by Rhizoctonia solani, is a major worldwide rice disease for which little is known about the molecular mechanisms of host immunity to infection. In the present study, a comparative proteomic analysis of two rice cultivars, Teqing (resistant) and Lemont (susceptible), inoculated with R. solani was conducted using an eight-plex iTRAQ (isobaric tags for relative and absolute quantitation) technique, resulting in the identification and quantification of 6560 proteins. A total of 755 proteins showed significant changes in abundance between plants infected with R. solani and control plants, based on an error factor < 2 and a more than 1.5-fold or less than 0.67-fold quantitative difference. The differentially abundant proteins were mainly involved in glyoxylate and dicarboxylate metabolism; glycine, serine and threonine metabolism; unsaturated fatty acid biosynthesis; and glycolysis/gluconeogenesis regulation pathways (p < 0.01). In addition, the expression levels of the genes encoding selected proteins were tested by qRT-PCR, and their functions were tested in Nicotiana benthamiana via agroinfiltration. Based on these proteomic and experimental data, a putative model of the regulation of rice immunity under R. solani infection is proposed. The proteins identified in the present study provide a basis for elucidating the molecular mechanisms underlying rice immunity to infection by R. solani.