Sarcoptes scabiei infection causes type I and IV hypersensitivity reactions induced by cytokines TGF-β and TNF-α. This study was conducted to analyze the TGF-β and TNF-α expression in rabbits with severe scabies. Five mixed-bred rabbits (3 males and 2 females), with age 12-18 months, were obtained from farms in East Java. Rabbit ear skin samples that showed clinical symptoms of severe scabies (without medical therapy), such as crusts, pus, excessive hyperkeratosis on nose, muzzle, around the eyes, ears and legs were collected. Skin scraping was done to detect the presence of S. scabiei mites, and skin samples were stained with hematoxylin eosin (HE) and subjected to immunohistochemistry. Strong staining of TGF-β and moderate staining of TNF-α were evident in all samples. TGF-β was expressed on stratum granulosum to stratum basalis of epidermis layer, half of the dermis, sebaceous gland, and hair follicle, while TNF-α was expressed on half of the epidermis layer, stratum spinosum to stratum basalis, and half of the dermis. This study illustrates that severe scabies infection triggered increased expression of TGF-β and TNF-α in rabbit ear skin, where TGF-β expression was more pronounced than TNF-α.