This work was carried out to study the response of four  Egyptian bread wheat cultivars i.e Giza 168, Giza 171, Sids 12 and Sids 13, to yellow rust disease and its effect on grain yield components under field condition at Nobaria Agriculture Research Station, during two growing seasons , (2015/16 – 2016/17). Results showed that there was a significant difference among the tested cultivars from the most of the studied yield parameters. Giza 171 had the highest significant values of days of heading plant height, grain yield, number of grain/spike and 1000 grain yield in the two seasons. On the other hand according to disease assessment Sids 12 had the highest significant values of final rust severity (FRS), rate of disease increase (r-value) and area under disease progress curves (AUDPC) in the two seasons. Inter-simple sequence repeat (ISSR) marker was used to measure the genetic diversity between one Stripe rust resistant wheat cultivar (YR7), the four local cultivated varieties and the F1 cross progeny. Ten ISSR primers were used, a total of 109 bands were amplified, among which 41 (37%) bands were polymorphic. The polymorphic bands amplified by each primer ranged from 2 to 8, with an average of 4.1. The genetic similarity ranged from 88% to 96%.