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Rice leaf folder, Cnaphalocrocis medinalis (Guenée), is one of the most serious pests on rice. At present, chemical control is the main method for controlling this pest. However, the indiscriminate use of chemical insecticides has non-target effects and may cause environmental pollution. Besides, leaf curling behavior by C. medinalis may indirectly reduce the efficacy of chemical spray. Therefore, it is crucial to cultivate efficient rice varieties resistant to this pest. Previous studies have found that three different rice varieties, Zhongzao39 (ZZ39), Xiushui134 (XS134), and Yongyou1540 (YY1540), had varying degrees of infestation by C. medinalis. However, it is currently unclear whether the reason for this difference is related to the difference in defense ability of the three rice varieties against the infestation of C. medinalis. To explore this issue, the current study investigated the effects of three rice varieties on the growth performance and food utilization capability of the 4th instar C. medinalis. Further, it elucidated the differences in defense responses among different rice varieties based on the differences in leaf physiological and biochemical indicators and their impact on population occurrence. The results showed that the larval survival rate was the lowest, and the development period was significantly prolonged after feeding on YY1540. This was not related to the differences in leaf wax, pigments, and nutritional components among the three rice varieties nor to the feeding preferences of the larvae. The rate of superoxide anion production, hydrogen peroxide content, and the activity of three protective enzymes were negatively correlated with larval survival rate, and they all showed the highest in YY1540 leaves. Compared to other tested varieties, although the larvae feeding on YY1540 had higher conversion efficiency of ingested food and lower relative consumption rate, their relative growth was faster, indicating stronger food utilization capability. However, they had a lower accumulation of protein. This suggests that different rice varieties had different levels of oxidative stress after infestation by C. medinalis. The defense response of YY1540 was more intense, which was not conducive to the development of the larvae population. These results will provide new insights into the interaction mechanism between different rice varieties and C. medinalis and provide a theoretical basis for cultivating rice varieties resistant to this pest. [ABSTRACT FROM AUTHOR]