Aims: Efflux transporters such as P-glycoprotein (Pgp; MDR1/ABCB1) protect the enterocytes from potentially toxic substances. The aim of this study was to evaluate Pgp expression in inflamed mucosa of patients with active Ulcerative Colitis (UC), and to compare the results of Pgp expression with healthy subjects. We also explored the relationship between Pgp expression and the pathogenesis of UC in this study. Methods: Pgp expression was determined with real-time PCR (SYBR GREEN), immunohistochemistry (IHC-SP method) and Western blot in inflamed mucosa of newly diagnosed (n = 102) patients with UC. Expression levels of Pgp expression were compared with control subjects (n = 31). The serum endotoxin and D-lactic acid levels of newly diagnosed UC patients and control subjects were detected by ELISA and ultraviolet spectrophotometer respectively. Results: Compared with control subjects, Pgp expression was significantly reduced in inflamed mucosa of newly diagnosed patients with UC. MDR1 (Multi-Drug Resistance 1) expression depicts a similar pattern. Pgp expression was found elevated in intestinal mucosa of UC patients after two months' treatment with prednisone. The serum endotoxin and D-lactic acid levels in UC patients before and after prednisone treatment were negatively relevant with Pgp expression level. Conclusions: Compared with healthy controls, the expression of Pgp was reduced in inflamed tissue of patients with active UC. The Pgp may play a role in the pathogenesis of UC.