OBJECTIVE: To investigate the effects of simvastatin on the proliferation of rat cardiac fibroblasts (CFs) induced by arginine vasopressin (AVP). METHODS: CFs of neonatal Sprague-Dawley (SD) rats were isolated by trypsin digestion method and growth-arrested CFs were stimulated with 1x10-7 mol/L AVP in the presence of simvastatin (Sim) with varied concentrations. MTT assay was employed to measure CFs proliferation and determine the cell number, and the cell cycle distribution was determined with flow cytometer (FCM). RESULTS: With the increase of Sim concentration, D490 of CFs as shown by MTT assay gradually decreased, and for the cells treated with 1x10-6 mol/L Sim or 1x10-5 mol/L Sim, D490 (0.215+/-0.041and 0.163+/-0.018, respectively) was significantly lower than that of the control (0.939+/-0.048, P<0.01). In a dose-dependent manner, Sim decreased the cell percentage at S stage and the proliferation index (PI) as its concentration increased, but acted to the contrary effect with the percentage of cells at G0/G1 stage, and in CFs treated with 1x10-5 mol/L or 1x10-6 mol/l Sim, the 3 parameters were significantly different from those measured in the CFs with 1x10-7 mol/L AVP treatment (P<0.01). CONCLUSION: The results indicate that Sim can inhibit the proliferation of CFs induced by AVP, possibly through the mechanism of regulating the cell cycle distribution.