The ideal barrier agent for the prevention of surgical adhesions has remained elusive. We have examined the ability of a new hydrogel N-O-carboxymethylchitosan, a derivative of chitin with properties similar to the extracellular matrix, to prevent adhesions when applied topically to traumatized mesothelial surfaces. In two rodent adhesion models (pericardial and peritoneal), the application of N-O-carboxymethylchitosan significantly prevented or minimized the formation of scar and fibrosis. According to a scoring system from 0 to 3 (0 = no adhesions and 3 = severe dense adhesions), control groups in each model consistently produced severe dense adhesions (2.9 +/- 0.2, 2.7 +/- 0.3). All treated groups consistently scored less than 1.0, indicating minimal or no fibrosis. The differences between the control and treated groups were statistically significant (p < 0.05). Thus, the application of N-O-carboxymethylchitosan to traumatized mesothelial surfaces may have significant potential in the prevention of postoperative adhesion formation.