Background: This study assessed the peritoneal fibrinolytic response during the first week after colonic surgery in rats with and without bacterial peritonitis, and possible modulation of the response by two hyaluronan-based antiadhesive agents. Methods: A colonic anastomosis was constructed in 90 male Wistar rats. Peritonitis was induced in another 108 rats and a colonic anastomosis was constructed after 24 h. Rats in both groups were randomized into an untreated group or one of two groups treated with hyaluronan-based agents. One-third of each group was killed at each of days 1, 3 and 7 after operation, and tissue plasminogen activator (tPA) antigen and activity were measured in peritoneal biopsies. Results: One day after colonic surgery in normal rats, tPA antigen concentration was significantly (P < 0.005) increased, whereas tPA activity levels were normal. By day 3 after operation tPA antigen had returned to baseline values while tPA activity was significantly increased (P < 0.05). One day after inducing peritonitis tPA antigen was significantly increased (P < 0.001), while tPA activity was significantly reduced (P < 0.05). Three and seven days after colonic surgery in rats with peritonitis tPA activity was increased (P < 0.001) while tPA antigen had returned to baseline values. Neither of the hyaluronan-based agents affected peritoneal tPA antigen levels or activity after colonic surgery. Conclusion: Both abdominal surgery and infection caused an early increase in peritoneal tPA antigen levels, followed by an increase in tPA activity. Peritonitis severely depressed early tPA activity. Application of hyaluronan-based agents did not affect the peritoneal fibrinolytic response to surgery and/or infection.