Interferon (IFN) interacts with endothelial cells and modulates the functions of these cells. In our study, we aimed to determine the effects of treatment with pegylated IFN-α (peg-IFN-α) on fibrinolytic parameters in patients with chronic hepatitis C. Fifteen patients with chronic hepatitis C were treated with peg-IFN-α once per week plus daily oral ribavirin. Euglobulin lysis time (ELT), plasma levels of D-dimer, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI) were determined before treatment, 2 weeks, 1 month, and 3 months after the initiation of the treatment. Plasma levels of t-PA increased significantly 1 month and 3 months after the treatment (P < .05). The PAI-1 and TAFI levels in 2 weeks, 1 month and 3 months after treatment were not statistically different as compared with pretreatment levels (P > .05) No significant difference in plasma D-dimer levels was observed during peg-IFN-α treatment (P > .05). There was a significant decrease in ELT 1 month and 3 months after the treatment (P < .05). Our results indicated that treatment with peg-IFN-α may be associated with enhanced fibrinolysis.