Harpophora maydis (formerly Cephalosporium maydis) is considered to be one of the most destructive pathogens causing late wilt disease of maize in Egypt. Therefore, the current investigation aimed to enlighten the relationship between the host (Zea mays) and the pathogenic agent (Harpophora maydis), included the chemical and histological differences between susceptible and resistant cultivars. Pathogen isolation was carried out through five Governorates in Egypt (Kafr El-Sheikh, El-Behera, El-Dakahlya, El-Menia and Sohage). Five obtained isolates differed in their virulence based on the pathogenicity test with five cultivars (SC.10, SC.123, TWC.310, Giza-2 and Balady). The maize cultivar (SC.10) was resistant to all the tested isolates. While the cultivar Balady showed the highest susceptibility. Isolate H. maydis No.5 isolated from Sohage Governorate was the most virulent isolate (disease incidence 25.75%), while isolate No.4 was the least virulent isolated from Menia Governorate (1.6%). Moreover, under artificial infection stress, linear increment of phenolic contents and total soluble sugars was observed with the resistant cultivar compared to susceptible one at 30, 60 and 90 days from planting. The obtained results showed highly significant (33.64 mg 10 g -1 fresh weight) with susceptible cultivars relative to resistant one (23.18 mg 10 g -1 ), for total soluble sugars contents.Also, results of phenolic contents gave a similar trend. For thickness of sheath bundle, thickness of the sheath-layer obviously increased with aging of plants, and thickness in both of resistant and susceptible cultivars was affected after infection process. Uninfected resistant plants showed increase in thickness of the scleronchymateous sheath-layer surrounding the vascular bundles compared with that of the susceptible uninfected plants. Consequently, phenolic contents may play an essential role in resistance process against late wilt disease as well as sugar contents with susceptibility process.