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Clusterbean in semi-arid regions suffers severely from blight and root rot diseases caused by Macrophomina phaseolina. Foliar spray and sorghum seed infection of this fungus activates the defense response in cluster bean. Changes in the phenolics and defense enzymes of guar leaves were compared by spray of fungal spore suspension and sorghum seed infection. Induction of infection in guar by either mode of infection showes a significant increase in the activities of polyphenols and phenylalanine ammonia-lyase (PAL). The investigation was carried in four cultivars of guar at different ages after different time intervals of infection. Result shows increase in activities of all defense related proteins to varying degrees at different stages of infection. Although both the inoculation methods were effective, but foliar application was found to be better mode of infection then sorghum grain infection in terms of rapid and enhanced PAL activity leading to the synthesis of phenolic compounds. Further, extent of defense response in RGC 1031 was more than that of rest three cultivars, which proves this cultivar was more potent in fighting against the invading pathogen. Thus there is a possibility of gene transfer from RGC 1031 to other cultivars. We demonstrate that the elevated levels of biochemicals, phenolic acids, and enzymes may play a major role in plant defense.