Abstract: Objectives To investigate the signal transduction pathway of hepatitis B virus X protein (HBx) in glomerular mesangial cell(GMC) TNF-α expression. Methods PCI-neo-X was transfected into cultured glomerular mesangial cells. TNF-α and its mRNA expression of GMC were compared between treated or untreated with ERKs inhibitor U0126, NF-κB inhibitor lactacystin and p38 inhibitor SB203580, respectively. HBx expression in glomerular mesangial cells was assessed by Western-blot. TNF-α mRNA expression was assessed by semi-quantitative RT-PCR. TNF-α levels in supernatants were measured by ELISA. Results HBx expression was found in transfected glomerular mesangial cells, and became prominent at 36 and 48 hours after transfection whatever with or without inhibitors in culture media. TNF-α mRNA expression was significantly decreased in U0126 or lactacytin group compared with U0126-free or lactacytin-free group. TNF-α levels in supernatants in pCI-neo-X transfection was also partially inhibited when treated with ERKs inhibitor U0126 or NF-κB inhibitor lactacystin, but no effect was observed in p38 inhibitor SB203580 treated group at 36 and 48h after transfection. Conclussion HBx upregulated TNF-α expression of GMC line partly through ERK1/2 and NF-κB signal transduction pathway, but not p38MAPK pathway.