A highly contagious skin condition called sarcoptic mange spreads through skin-to-skin contact. This study aims to evaluate the health status of rabbits with Sarcoptes scabiei regarding lesion score concerning treatment trials using Neem extract evaluation of physiological parameters. From August 2022 to August 2023, 200 domestic rabbits were examined carefully for the presence of mange in their bodies, lesion scores were recorded, as was the collection of sera for biochemical analysis with infested skin and spleen from the infested animals. The infested rabbits were classified into eight groups (6 groups with lesion scores from 0-5): negative control rabbits with no lesion, normal control rabbits, and positive control rabbits treated with Ivermectin alone. Every group has ten rabbits. Serum nitric oxide (NOx) and major histocompatibility class I (MHC-I) were evaluated. The affected rabbits suffered from malnourishment and emaciation. There were also indications of scratching, itching, fur loss, hyperemia, and skin thickening with crust formation. Serum nitric oxide was evaluated according to lesion score, a score of 0 was negative and healthy, and then the nitric oxide (NOx) serum levels were elevated according to the increase in the severity of the diseases with lesion score, this NOx was lower after treatment. Measurable quantities of MHC-I mRNA were examined in each group's lesion score in the skin or spleen. The spleen expression profile was higher in all groups than in the skin. With the increase in the score, the transcript levels increase. This MHC-I level was lower after treatment. Conclusion: The infestation with scabies in rabbits elevated the stress factor, which was then downregulated using one of the eco-friendly agents against these parasites, which had no resistance in rabbits.