The effects of chronic fluoride exposure on kidney integrity and histological structure, along with effects on associated enzymes and metabolite changes, were investigated in young pigs. Twenty-four crossbred barrows (Duroc×Landrace×Yorkshire) about 50 days old were randomly divided into three groups of eight pigs each. Groups I, II, and III received the same basal diet additionally supplemented, respectively, with 0, 100, and 250 mg F–/kg (from NaF). Results obtained after 50 days indicated that supplemental fluoride-treatment caused severe renal histological changes as well as increased renal cell apoptosis. In kidney tissue, lactate dehydrogenenase (LDH) activity was significantly increased in group III, whereas alkaline phosphatase (AKP) activity was significantly decreased in group II as well as in group III. In the serum, significantly increased urea nitrogen (UN) was present in groups II and III, and the serum of group III had elevated creatinine (Cre) and decreased Na+. These findings show that chronic excessive fluoride exposure is deleterious to kidney structure and function of pigs.