Rabbit mange called rabbit plaque, it is a contagious disease affects all rabbits in the farm, spread rapidly and characterized by pruritus, alopecia, and crust formation on the legs, lips, ears or different parts of the body. This disease lead to severe economic losses include weight loss, reduced production, medication cost, misshaped rabbit, and mortality. In spite of many topical medications were used for treatment of rabbit mites, there were no satisfied results as well as the irritant effect of some of them, in addition to the long withdrawal time and drug residue of ivermectin injection so this study tried to apply a new approach to use an Ivermectin carried on glycerin as a topical treatment to overcome the side effect of other treatments. In this study fourty two rabbits naturally infested with mange were divided into seven groups (six rabbits/each),  1^st group treated with Ivermectin 1% injection, 2^nd group treated with topical Ivermectin 0.05%, and 3^rd group treated with topical Ivermectin 0.1%, 4^th group treated with topical Ivermectin 0.15%, 5^th group treated with topical sulphur 15%, 6^th group treated with topical cibermethrin 10%, and 7^th group treated with topical cebacil gel (phoxim 50%). All rabbits were observed daily recording recovery and mortality rate, skin lesions sent for histopathology, and serum samples were taken at 0, 4, 8, 15, 22 days post treatment to measure Total protein, Albumin, Creatinine, Glucose, Cu, Zn, Fe, SOD and MDA. Our findings showed Cebacil gel caused 100% mortalities, so it should be excluded where it was toxic if used more than two days post treatment, Ivermectin 0.1% produced significant body weight changes when compared with control groups, Ivermectin 1% injection, and topical sulphur 15% while the remaining treatments produced non-significant body weight changes with an improvement of all biochemical blood parameters including SOD, MDA, Fe, Cu, Zn, Tp, Alb, Crea, and Glu.. Ivermectin 0.1% recorded 100% survival, no persistent skin scales, and the highest reduction rate of damaging indicator, SOD, while the other treatments revealed persistent skin scales and/or mortalities, so Ivermectin 0.1% was preferred as drug of choice for topical treatment of external mange in rabbits