Background/Aims: Cellular hypertrophy is an early important pathological feature of renal diseases such as diabetic nephropathy and remnant kidney. Recent studies have demonstrated that angiotensin II (Ang II) might be a major contributor in regulating cell hypertrophy. However, the exact mechanism is still unclear. The aim of our present work was to investigate the possible role of a newly clarified fibrogenic factor, connective tissue growth factor (CTGF), in mediating the effect of Ang II-induced tubular cell hypertrophy. Methods: The cell line HK2 was grown in Dulbecco’s modified Eagle’s medium containing 10% heat-inactivated fetal calf serum. After the cells were rested in serum-free medium for 24 h, the dose and time response of CTGF mRNA expression to Ang II stimulation was observed by RT-PCR, and protein synthesis was observed by Western blotting. The effect of anti-CTGF on Ang II (10<sup>–7</sup> M)-induced [<sup>3</sup>H]-leucine incorporation, total protein content (Coomassie brilliant blue G250 method) and change in cellular size [determined by a scanning electronic microscope (SEM)] was also observed. The influence of anti-CTGF antibody on the cell cycle was analyzed by using a fluorescence-activated cell sorter flow cytometer. Results: The results showed that Ang II induced expression of CTGF mRNA in a time- and dose-dependent manner (p < 0.05 and 0.01, respectively). Stimulation of cells with Ang II (10<sup>–7</sup> M) for 48 h resulted in a 92% increase in [<sup>3</sup>H]-leucine incorporation (5,584 cpm/10<sup>5</sup> cells at 0 h vs. 10,741 cpm/10<sup>5</sup> cells at 48 h; p = 0.01), which was significantly abolished by treatment with anti-CTGF antibody. Ang II (10<sup>–7</sup> M) significantly increased the total protein content in HK2 cells (control: 0.169 ± 0.011 mg/10<sup>5</sup> cells vs. Ang II: 0.202 ± 0.010 mg/10<sup>5</sup> cells; p = 0.03), which was markedly inhibited by cotreatment with anti-CTGF antibody. The average cellular diameter determined by SEM showed that the increase in cell size induced by Ang II could be significantly inhibited by anti-CTGF antibody (control: 11.92 ± 1.62 µm, Ang II group: 20.63 ± 3.83 µm, Ang II + anti-CTGF group: 16.43 ± 3.23 µm; p < 0.01, respectively). Furthermore, the flow cytometer study showed that Ang II arrested the cell cycle at G0–G1 phase, which was significantly reversed by treatment with anti-CTGF antibody (G0–G1 percentage: in Ang II group: 76 ± 1.8%, in Ang II + anti-CTGF group: 71 ± 1.78%; p = 0.04). Conclusion: Our data are the first to clearly demonstrate that CTGF might be an important mediator of Ang II-induced renal hypertrophy, which suggests that inhibiting the production of CTGF might be the new strategy in early prevention of renal fibrosis.