The present study included 719 cats admitted to the teaching veterinary hospital, the faculty of veterinary medicine, Cairo University, and private clinics. All cats were from different breeds, sexes, and ages. This number was divided into 488 diseased and 231 apparently healthy cats. 128 (26.2%) cases were recorded with different hepatopathies from the diseased number. Feline cholestasis was detected in 32 cases (25%). The present study gathered 52 cats (32 cases with cholestasis and 20 healthy cats). Comprehensive clinical, ultrasonographic, and Hemato-biochemical investigations besides hepatocyte-derived miRNA-122 evaluation were conducted on all animals. Feline cholestasis was mostly detected in mixed breed cats older than 3 years, more in tom cats than queens. The most recorded clinical signs were icteric mucous membranes, yellow skin, anorexia, cranial abdominal pain, vomiting, and diarrhea. The recorded causes of cholestasis were biliary sludge, cholecystitis, hepatic lipidosis, and cholangitis. Descriptive ultrasonographic findings were also included. Regarding cats with cholestasis, Physical examination showed significant elevation in respiration and pulse rates. The hematological evaluation showed significant anemia with elevation of absolute neutrophilic count. Serum biochemistry revealed significant elevation in all hepatic function enzymes and bilirubin. Also, a significant decrease was recorded in potassium levels. Hepatic biomarker (miRNA-122) fold expression recorded a significant increase in diseased cats indicating a close association between cholestasis and hepato-biliary cellular injury. Mi-RNA-122 was a specific and early predictor of inflammatory reactions of varying degrees. This made it of major clinical significance in the diagnosis of cholestasis in cats.