Renal repair begins soon after the kidney suffers ischemia-reperfusion injury (IRI); however, its molecular pathways are not fully understood. Clusterin (CLU) is a chaperone protein with cytoprotective functions in renal IRI. This study investigated the role of CLU in renal repair after IRI. IRI was induced in the left kidneys of wild type (WT) C57BL/6J (B6) versus CLU knockout (KO) B6 mice by clamping the renal pedicles for 28 - 45 min at the body temperature of 32oC. The renal repair was assessed by histology and confirmed by renal function. Gene expression was examined using PCR array. Here, we showed that following IRI, renal tubular damage and CLU expression in WT kidneys were induced at day 1, reached the maximum at day 3 and significantly diminished at day 7 along with normal function, whereas the tubular damage in CLU KO kidneys steadily increased from initiation of insult to the end of experiment when renal failure occurred. Renal repair in WT kidneys was positively correlated with an increase in Ki67+ proliferative tubular cells and survival from IRI. The functions of CLU in renal repair and renal tubular cell proliferation in cultures were associated with up-regulation of a panel of genes that could positively regulate cell cycle progression and DNA damage repair, which might promote cell proliferation but not involve cell migration. In conclusion, these data suggest that CLU is required for renal tissue regeneration in the kidney repair phase after IRI, which are associated with promotion of tubular cell proliferation.