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AIM: To investigate the effect of polaprezinc on cellular damage induced by hydrogen peroxide (H2O2) in human colon CaCo2 cells.METHODS: CaCo2 cells were treated with polaprezinc (10-100 μmol/L) for 6 h. After polaprezinc treatment,the cells were incubated with H2O2 (20 μmol/L) for 1 h.Cell viability was measured by MTT assay. West blot analysis for heat shock protein (HSP) 27 and HSP72 in the cells was performed. Moreover, cells were pretreated with quercetin (200 μmol/L), an inhibitor of HSP synthesis, 2 h before polaprezinc treatment, and cell viability and the expression of HSP27 and 72 were assessed in these cells.RESULTS: Polaprezinc significantly protected CaCo2 cells from cell damage induced by H2O2, and up-regulated the expressions of HSP27 and HSP72 in the cells (10, 30and 100 μmol/L of polaprezinc; 35.0% ± 7.7%, 58.3% ±14.6% and 64.2% ± 8.2%, respectively. P ＜ 0.01 versus polaprezinc-nontreated cells; 6.0% ± 4.4%). Quercetin inhibited the up-regulation of HSP27 and HSP72 by polaprezinc and diminished the protective effect of polaprezinc against H2O2-caused injury in the cells.CONCLUSION: Polaprezinc is a useful therapeutic agent for treatment of colitis and its effects depend on the function of cytoprotective HSP in colon.