This work was carried out in disease nursery at Gemmeiza  Agricultural  Research Station, El-Gharbeia Governorate, Egypt in 2009 and 2010 growing seasons. Five grain sorghum cultivars i.e. Isis, Horas, Zosar, Giza 15 and Giza 113 were evaluated for downy mildew disease resistance caused by Peronosclerospora sorghi. Effect of downy mildew disease on grain yield and leaves chemical components was also studied.  The tested grain sorghum cultivars were varied significantly in their response to downy mildew disease. The cultivars Isis and Zosar were showed as highly resistant. Horas cv. was classified as moderately susceptible. While, Giza 15 and Giza 113 were classified as susceptible. The highly resistant cultivars Isis and Zosar showed the highest grain yield, in addition the leaves of these varieties contained the highest level of total nitrogen, crude protein , phosphorus and potassium compared with the susceptible cultivars. The enzymatic activity of peroxidase and polyphenoloxidase and also, phenolic compounds contents in the grain sorghum cultivars leaves were the highest in case of the highly resistant cultivars. The leaves of susceptible cultivars showed the lowest contents of enzymatic activity and phenolic compounds. Results showed a positive correlation between the resistance degree and grain yield and / or chemical components.