Objectives To investigate the effects of nano-carrier G9 PAMAM mediated plasmid containing the CTGF-shRNA (pCTGF-shRNA) on the expression of CTGF in mouse peritoneal mesothelial cells. Methods The plasmids named pCTGF1-shRNA、pCTGF2-shRNA and negative control pHK-shRNA were designed and formed. Transfection of plasmids to MPMCs (3rd generation, induced by 4.25% glucose) was performed using G9 PAMAM. The expression of CTGF mRNA was detected by RT-PCR. The protein level of CTGF was determined by Western Blot. Results With the treatment of 4.25% glucose, the expression of CTGF in MPMCs were significantly up-regulated. Introduction of pCTGF1-shRNA and pCTGF2- shRNA resulted in significant reduction of CTGF expression (P<0.05) with pCTGF2-shRNA more effective. But the introduction of pHK-shRNA did not lead to significant reduction in CTGF expression（P>0.05）. Conclusions Nano-carrier G9 PAMAM has the ability to efficiently transfect pCTGF-shRNA into primary MPMCs and has prominent inhibition effects on increased expression of CTGF induced by high glucose. PAMAM vector mediated pCTGF-shRNA can be used as a very efficient strategy in gene therapy of peritoneal fibrosis