We studied the role of selective suppression of liver Kupffer cells (gadolinium chloride, 14 mg/kg intravenously) in the development of intrahepatic cholestasis in CBA/C57B1/6 mice after intraperitoneal injection of alpha-naphthylisothiocyanate in a single dose of 200 mg/kg. Pretreatment with gadolinium chloride increased the severity of cholestasis and signs of liver damage. Gadolinium accumulation in the liver peaked after 24 h and was accompanied by a decrease in activities of cathepsin D and cathepsin B and concentration of matrix metalloprotease-2. Our results confirm the hypothesis that normal function of Kupffer cells and extracellular matrix plays an important role in cholestasis. Administration of gadolinium chloride serves as a convenient model to study the side effects, toxicity, and safety of lanthanides as nanoparticles.