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AIM: To elucidate the metabolism and the effect of the cydosporin A (CyA) as a representative immuno-suppressive drug used in transplantation in a partially hepatectomized rat model. METHODS: CyA was administered to rats that under-went a 70% hepatectomy. These rats were randomly assigned into three groups according to the dose of CyA administration as follows; (group 1) water, (group 2) 5 mg/kg CyA, (group 3) 10 mg/kg CyA. On post-operative days-1, 3, 7 and 14, the rats were killed to analyze the serum concentration of CyA, the liver re-generation ratio, biochemical or histological markers, and mRNA expression using reverse transcriptase-poly-merase chain reaction method to determine albumin and cytochrome p450 expression. RESULTS: The serum concentration of CyA in group 3 was significantly higher than group 2 during liver regeneration. CyA enhanced the liver regeneration in a dose dependent manner. The mRNA expression associ-ated with CyA metabolism was significantly decreased on day 14, while preserving the albumin producing activity. CONCLUSION: These data indicate that the 10-450 ac-tivity required to metabolize the CyA may be reduced during regeneration of the remnant liver after a hepa-tectomy, which may, therefore, be linked to difficulty in controlling the optimal dose of CyA during early period of LDLT.