To observe the characteristics of primary biliary cirrhosis (PBC) with a suboptimal biochemical response to ursodeoxycholic acid. A total of 38 Chinse PBC patients (5 male patients, 33 female patients, average age 55 years old) with treatment of ursodeoxycholic acid in our hospital from January 1999 to January 2009 were erolled and studied retrospectively. 17 suboptimal biochemical responders mainly presented with liver diseases related symptoms including jaundice (41.1%), fatigue, anorexia (23.5%), edema and abdominal distension (11.7%). 21 good biochemical responders mainly presented with abnormal liver function tests without symptoms. The suboptimal biochemical responders had significantly higher baseline levels of total serum bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, immunoglobulin G and globulin as compared to the good biochemical responsers. There were no differences in gender, age and the dose of UDCA. PBC patients with liver diseases related symptoms, marked abnormal liver tests and characteristics of autoimmune hepatitis may have a suboptimal biochemical response to ursodeoxycholic acid treatment.