The effect of chitosan on tight junctions (TJs) permeability on Caco-2 cell monolayer intestinal model was investigated. We have also investigated the effects of low molecular weight water-soluble chitosan (LMWC) on apoptosis in HT-29 cell. The changes in barrier properties of Caco-2 cell monolayers, including transepithelial electrical resistance (TEER) and permeability to lucifer yellow, were assessed in response to chitosan treatment. High molecular weight chitosan (HMWC) was found to cause up to 50% dose-dependent reduction in TEER of Caco-2 cell monolayer without damage to the cell membrane under lower concentration. The effect of HMWC on TJs was confirmed by increased permeability of lucifer yellow when cells were treated with 0.001-0.0001% HMWC for 120 min compared to control cells. Results showed that HMWC did not affect the F-actin of cytoskeleton. LMWC was proven to be an antitumor compound as shown by inducing apoptosis as a function of DNA fragmentation. These results suggest that HMWC is an useful drug delivery agent in paracellular pathway and LMWC has potential value in colon cancer therapy.