Objectives To determine the effects of Matrine (Ma) on signal transducers and activators of transcription (STAT) 1, 3, connective tissue growth factor (CTGF) and platelet -derived growth factor (PDGF) in glomerular mesangial cells (MC) induced by lipopolysaccharide (LPS), and to explore the protective mechanisms of Ma. Methods Ma were added to cultured glomerular mesangial cells which were exposed to LPS for 12, 24 and 48 hours. Real time polymerase chain reaction were used to determine STAT1, 3, CTGF, PDGF mRNA, The protein expression of STATI, 3 and p-STAT1, 3 were observed by Western blot. Results Compared with the control group, MC proliferation of the LPS group (10μg/ml) significantly increased, which were suppressed in the Ma (320 μg/ml) group (P < 0.01) at 12, 24, 48 hours. The expression of STAT1, 3, CTGF, PDGF mRNA and the levels of p-STAT1 , p-STAT3 protein was significantly increased in MC under LPS medium at 12, 24, 48 hours, which were obviously lower in Ma group than those of the LPS group, especially at 24, 48 hours. Conclusions The protective mechanisms of Matrine is considered to down-regulate the expression of STAT1, 3, CTGF and PDGF.