Background:  Ursodeoxycholic Acid (UDCA)is a highly hydrophilic bile acid,which dissolves cho- lesterol and fat in the intestines,and has immune modulating factor.It is an approved drug that may limit liver injury in HCV infection. Objective: The aim of this study is to evaluate the efficacy of UDCA on serum alanine aminotrans- ferase (ALT),gamma-glutamyl transferase (GGT),and HCV-RNAlevel in patients with Chronic Hepatitis C (CHC) who had not responsed or had relapsed to interferon (IFN)monotherapy or IFN or pegylated interferon alpha (PEG IFN-µ)plus ribavirin treatment. Patients and Methods: Eighteen patients who had not responsed or had relapsed to IFN monotherapy or IFN or PEG IFN-µ plus ribavirin treatment were randomized to receive UDCA (250 mg,tid)(n =10)or placebo (n =8)for 6 months. Results: At 3-month serum ALT level was significant decrease in the UDCA group as compared with placebo and baseline (p =0.041 and p =0.022,respectively).There was no significant changes in the serum ALT, GGT, and HCV-RNA level at the end of the 6-month treatment period in both groups. Conclusions: We report preliminary results of a trial using UDCA in treatment of non-responder or relapser CHC. UDCA is effective in term of ALT level but not in term of the virologic response and GGT.  These results favor the hypothesis that UDCA may have direct cytoprotective effects on the hepatocyte.  UDCA may be a possible alternative for patients who do not response or has relapsed after discontinuation of IFN monotherapy or IFN or PEG IFN- µ plus ribavirin treatment.