The resistance to sesame leaf spot disease of 20 main rice varieties and 5 control varieties in Sichuan Province was evaluated with potted plant disease resistance identification method to study the resistance to sesame leaf spot disease and the physiological and biochemical mechanisms of disease resistance in the main rice varieties in Sichuan Province. The activity of 5 defense enzymes was determined in the leaves of different resistant varieties. The secondary metabolites in the leaves of rice seedlings in resistant and susceptible varieties were analyzed with gas chromatography/mass spectrometry （GC/MS）. The results showed that Yuxiangnuo 1 and Zhejingyou 4 were highly resistant varieties，while 5 varieties including Xiushui 134，Zhehe 622，Zhehexiang No.2，Zhejingyou 77 and Zhejingyou 1578 had moderate resistance，and the rest were susceptible varieties. The activity of 5 enzymes including superoxide dismutase （SOD），polyphenol oxidase （PPO），phenylalanine ammonia lyase （PAL），peroxidase （POD），and catalase （CAT） increased first and then decreased in both resistant and susceptible rice varieties，but the activity of enzyme in resistant varieties was significantly higher than that in susceptible varieties. A total of 18 secondary metabolites were obtained，among which 4 metabolites including ribosyl alcohol，D-glucose，malic acid，and 2，3，4-trihydroxybutyric acid had significant differences in content between resistant and susceptible rice varieties，and between inoculated and non-inoculated treatment of the same variety. It is indicated that rice resistant varieties can resist the invasion of sesame leaf spot disease by increasing the activity of 5 defense enzymes and the content of four secondary metabolites.