Sheath blight of rice, caused by Rhizoctonia solani, is one of the most devastating rice diseases worldwide. No rice cultivar has been found to be completely resistant to this fungus. Identifying antioxidant enzymes activities (activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)) and malondialdehyde content (MDA) responding to sheath blight infestation is imperative to understand the defensive mechanism systems of rice. In the present study, two inoculation methods (toothpick and agar block method) were tested in double-season rice. Toothpick method had greater lesion length than agar block method in late season. A higher MDA content was found under toothpick method compared with agar block method, which led to greater POD and SOD activities. Dense planting caused higher lesion length resulting in a higher MDA content, which also subsequently stimulated higher POD and SOD activity. Sheath blight severity was significantly related to the activity of antioxidant enzyme during both seasons. The present study implies that rice plants possess a system of antioxidant protective enzymes which helps them in adaptation to sheath blight infection stresses. Several agronomic practices, such as rational use of fertilizers and optimum planting density, involved in regulating antioxidant protective enzyme systems can be regarded as promising strategy to suppress the sheath blight development.