Abstract: The study aim to evaluate crude and two fractionated gut extract antigens of engorged females of Hyalomma dromedarii for protection against tick-feeding. To obtain the two fractionated gut extract antigens (FGE1 and FGE2) from Crud Gut Extract (CGE), gel filtration was used. CGE, FGE1 and FGE2 were used as immunogens for rabbits with Freund`s adjuvant. Six immunized and two control groups were challenged with adult and larvae of H. dromedarii (3 immunized and 1 control for each stage). Results showed that the efficacy of immunogens against adult (E%) showed that FGE1 recorded the highest immune effects on the adults (64.97%) followed by CGE which recorded (30.97%) and the lowest protection recorded with FGE2 (21.57%), while E% of CGE, FGE1 and FGE2 were 85.01, 82.13 and 70.1%, respectively, on larvae. The results of Enzyme Linked Immunuosorbent Assay (ELISA) revealed that the level of antibodies for all tested antigens increased gradually until the date of challenge with ticks and then declined. Western blot technique for both adults and larvae showed that the antigen CGE revealed two reactive bands at molecular weights of 50 and 34 kDa before challenge with ticks. These bands still to be reactive after challenge with ticks. Meanwhile, before challenge, the antigen FGE1 exhibited 3 reactive bands with molecular weights 145.89, 61.09 and 24 kDa and one band at molecular weight of 34 kDa after challenge with ticks. Moreover, the antigen FGE2 had only one reactive band at molecular weight of 34 kDa before challenge with ticks and two reactive bands at molecular weight of 34 and 24 kDa after challenge with ticks.