Abstract: In order to investigate the co-effects of compound microbial inoculum and organic-inorganic fertilizer on the resistance, growth, yield and quality of flue-cured tobacco, the activity of various defensive enzymes in tobacco roots and leaves at different growing stages as well as the changes of tobacco yield and quality were determined with field trials. The results indicated that proportionate application of compound microbial inoculum with organic and inorganic fertilizers significantly improved the agronomic character of tobacco, enhanced the activities of defensive enzymes, such as superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and phenylalanine ammonia lyase (PAL) in tobacco roots and leaves, and reduced the morbidity and disease index relative to tobacco black shank disease, tobacco mosaic virus disease and tobacco brown spot disease. Correlation analysis showed that the activities of defensive enzymes (PAL, SOD, and POD) in tobacco roots positively correlated to those in tobacco leaves. Proportionate application increased the contents of total sugar and reducing sugar in tobacco leaves, especially increased potassium content significantly, which made the chemical composition in tobacco leaves more harmonious. The experiments indicated that the application of compound microbial inoculum together with 75% organic and inorganic fertilizers was beneficial to the growth, development of flue-cured tobacco and increasing its yield, quality and resistance to stress.